Tramadol: Uses, Side Effects, Dosage, and Risk

Tramadol is a synthetic opioid analgesic medication used to treat moderate to moderately severe pain in adults and adolescents 12 and older. Tramadol—also sold as brand names ConZip, Ryzolt, and Ultram—belongs to the partial opiate agonist drug class. These drugs bind to opioid receptors in the brain to provide pain relief.

Tramadol may have a useful place in your treatment regimen, but it's critical that you are fully informed about the drug before you use it due to the risk of dangerous and life-threatening side effects. The U.S. Drug Enforcement Administration listed Tramadol as a schedule 4 controlled substance in August 2014 due to the risk of addiction and overdose.

Tramadol comes in extended-release capsules, extended-release tablets, and a topical cream named EnovaRX-Tramadol.

Tramadol Uses

Tramadol decreases the body's ability to feel pain. It works similarly to morphine, but tramadol is about one-tenth as potent.

Tramadol is used for moderate to moderately severe pain conditions, such as neuropathic pain (nerve pain) or osteoarthritis pain. It may also be prescribed for low back pain or rheumatoid arthritis.

Immediate-release tramadol tablets can be used for acute pain, while extended-release capsules and tablets are usually used to treat chronic pain when continuous treatment is needed.

Topical tramadol may be prescribed for people with musculoskeletal pain.

Tramadol is not approved for children under 12, as they are at greater risk of experiencing drug-induced breathing problems and death compared to older children and adults.

Off-Label Uses

Tramadol is sometimes used off-label as a treatment for premature ejaculation, but the risk of addiction means it is not a long-term treatment option.

Before Taking Tramadol

Tramadol is not a first-line treatment for pain since it carries serious addiction, overdose, and death risks. The drug is prescribed as a second-line or alternative treatment after other drug options, such as non-opioid analgesics, have been ineffective or inadequate in managing pain.

All opioids carry the risks of addiction, abuse, and misuse, even at recommended doses. But compared to immediate-release opioids, there is an increased risk of overdose and death with extended-release opioid drugs such as tramadol, due to the larger amounts of tramadol they contain.

Slow-release capsules are gradually absorbed, reaching lower peak blood concentrations than the slow-release tablets, so sometimes tramadol capsules might be preferred to tablets.

As with all Schedule IV controlled substances in the U.S., after a prescription is first written, you can get a maximum of five refills in a six-month period. After you hit that limit or reach the six-month mark (regardless of the number of refills), a new prescription is required from your healthcare provider.

Talk to your healthcare provider about all medications, supplements, and vitamins that you currently take. While some drugs pose minor interaction risks, others contraindicate use or prompt careful consideration.

Precautions and Contraindications

Tramadol can have severe and life-threatening side effects, including respiratory depression (impaired breathing), so your healthcare provider will do a full medical and mental health history and physical examination before prescribing it to you.

Be sure to tell your healthcare provider about any respiratory conditions or personal or family history of alcohol or drug addiction.

Tramadol should not be used if any of the following apply:

• Allergy or hypersensitivity: Do not take tramadol if you have a known allergy or hypersensitivity to tramadol or other opioids.
• Risk factors for respiratory depression (adolescents): Those ages 12 to 18 who have additional risk factors, such as respiratory impairment, should not take tramadol. This includes those recovering from surgery and those with obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, or taking other medications that can cause respiratory depressive effects. 
• Tonsillectomy or adenoidectomy before age 18: Tramadol is not approved for managing pain after surgical removal of the tonsils and/or adenoids in those younger than 18.
• Pregnancy: Use during pregnancy can cause neonatal opioid withdrawal, which can become life-threatening to the infant if it's not recognized and treated.
• Breastfeeding: Tramadol is not recommended for nursing mothers, as the drug can be passed on through breast milk, possibly causing respiratory harm to infants.
• Pre-existing respiratory depression: If you have pre-existing respiratory depression, the use of opioids increases your risk of respiratory arrest and death.
• Gastrointestinal obstruction: Do not take tramadol if you have a known or suspected gastrointestinal obstruction or paralytic ileus (lack of movement through the intestines).
• Seizures: there is an increased risk of seizures associated with this medication. If you have a prior history of seizures or a condition that might predispose to a seizure (such as a serious head injury in the past), talk with your healthcare provider before taking this medication.
• Suicide risk: Tramadol should not be used in patients who are suicidal or have a history of suicidal thoughts.

There are additional medical circumstances that can make taking tramadol risky or prohibit its use, including:

• Personal or family history of addiction or substance abuse: Risks for addiction, abuse, and misuse increase for those who are prone to addiction.
• Asthma: Those with acute or severe bronchial asthma are at risk of respiratory distress. Do not take tramadol in an unmonitored setting or without resuscitative equipment if you have asthma.
• Chronic pulmonary disease: Patients with chronic obstructive pulmonary disease (COPD) or cor pulmonale (right-sided heart failure), and those with a decreased respiratory reserve, hypoxia (low oxygen), or hypercapnia (excess carbon dioxide), are at increased risk of respiratory problems, including apnea (pauses in breathing)—even when tramadol is taken at recommended doses.

Other Partial Opioid Agonists

Tramadol's active form is O-desmethyltramadol (M1), which partially acts on opioid receptors. Other partial opioid agonists include:

• Sublocade (buprenorphine)
• Butorphanol
• Pentazocine

Full opioid agonists, such as morphine, codeine (codeine is metabolized into morphine), and OxyContin (oxycodone), bind more firmly to opioid receptors for stronger effects.

Tramadol Dosage

Due to tramadol's risks of addiction, it is important to use the lowest effective dosage for the shortest duration possible, as recommended by your healthcare provider.

Tramadol comes in 100-, 200-, and 300-milligram (mg) capsules. It can also be prescribed as an immediate-release 50-mg tablet or as an extended-release 100-, 200-, or 300-mg tablet.

The topical cream starts as a powder that is mixed into a base for application; the mixing is typically done by a healthcare provider or pharmacist.

The starting dose for extended-release tramadol is 100 mg. It may be increased in 100-mg increments every five days up to a maximum daily dose of 300 mg.

The half-life of tramadol in the blood is typically between five and nine hours, and even longer for people who have been taking multiple doses. This is the time it takes half of a dose to be inactivated by the body. Complete elimination takes about five to six times as long as the half-life.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Do not take two doses or you will be at risk of overdose.

All listed dosages are according to the drug manufacturer. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

Modifications

Respiratory depression is more likely in elderly, frail, or debilitated patients because they may not clear the drug as quickly as younger, healthier people. There is also the dangerous risk of drug interactions for older people who take other medications.

The risks of sedation and respiratory depression are also increased in anyone with head injuries, brain tumors, or increased intracranial pressure.

If you have these risks, you may need to take lower doses of tramadol and will need to be monitored more closely when using it.

Both poor and rapid metabolizers of tramadol may need dosage adjustments or to stop taking the drug completely.

• Some people, based on their genetics, process tramadol slowly. It is estimated that about 7% of people take longer to break it down and are described as "poor metabolizers" of tramadol. As a result, they have more of the active drug in their bloodstream for a longer time. Poor metabolizers are especially at risk if taking other medications that further reduce the actions of the enzymes that break down tramadol.
• Up to 10% of people are inherent "ultra-rapid metabolizers" of the drug, meaning they convert tramadol into its active metabolite more rapidly and completely. This rapid conversion results in higher than expected blood levels of the drug, which can lead to life-threatening or fatal respiratory depression or signs of overdose.

How to Take and Store

Take your medication exactly as directed. Take tramadol with a glass of water at scheduled times. You can take it with or without food.

Swallow your tramadol pills whole and do not split, chew, crush, dissolve, snort, or inject extended-release tablets. Breaking the pill may cause too much of the drug to be released into your system at one time, which could lead to overdose or death. 

Store the medication at room temperature between 68 to 77 degrees F. Keep it separate from other medications and out of reach of children.

Accidental ingestion of even one dose of tramadol can result in a fatal overdose.

Tramadol Side Effects

Tramadol is usually well-tolerated when taken properly. Side effects are usually temporary, but there is a risk of very serious adverse effects that can be deadly. Let your healthcare provider know if you have any side effects while taking tramadol.

Common

Common side effects of tramadol may include:

• Nausea
• Constipation
• Dry mouth
• Drowsiness
• Dizziness
• Vomiting
• Headache

Severe

Seek urgent medical help if you have any of the following symptoms while taking tramadol:

• Slowed breathing
• Shortness of breath
• Fast heartbeat
• Chest pain
• Swelling of your face, tongue, or throat
• Skin reactions
• Extreme drowsiness
• Lightheadedness when changing positions
• Feeling faint
• High body temperature
• Trouble walking
• Unexplained stiff muscles
• Mental changes, such as confusion or agitation
• Seizures
• Angioedema (fluid swelling under the skin)
• Suicidal thoughts or actions

Symptoms of tramadol withdrawal include:

• Restlessness
• Muscle and bone pain
• Insomnia
• Diarrhea
• Vomiting
• Cold flashes with goose bumps
• Leg movements

Tramadol Interactions and Warnings

A 2015 government report showed a steep rise in emergency room visits due to tramadol abuse between 2005 and 2011. Even at prescribed doses, the drug can be addictive.

If you suspect you are becoming dependent on tramadol or taking more than prescribed to get the desired effect, get professional guidance to wean off the medication, (as well as alternatives for pain relief).

In addition to addiction risks, there are other serious health conditions that can occur while taking tramadol, including: 

• Serotonin syndrome: Do not take tramadol if you have taken MAOIs, such as Nardil (phenelzine), Parnate (tranylcypromine), or Zyvox (linezolid), within the last 14 days. The interaction can lead to life-threatening complications such as serotonin syndrome or opioid toxicity. Serotonin syndrome can be life-threatening, so you should seek urgent medical care if you suspect it. Symptoms include muscle rigidity, confusion, and rapid heart rate.
• Opioid toxicity: This may lead to respiratory depression or coma.
• Seizures: Taking tramadol can lead to seizures, especially at higher-than-recommended doses and in patients with epilepsy, a history of seizures, or a high risk of seizures (such as due to head trauma, metabolic disorders, or alcohol or drug withdrawal). Seizure risk also increases if you are taking other drugs that reduce the seizure threshold in addition to tramadol.
• Adrenal insufficiency: Opioids inhibit the adrenal glands from producing enough of certain hormones. Symptoms tend to come and go and include abdominal pain, dizziness, extreme fatigue, and weight loss. If you are diagnosed with adrenal insufficiency, you will need to be slowly weaned off tramadol.
• Severe hypotension (low blood pressure): Hypotension can begin with dizziness and weakness. If severe enough, it can lead to heart or brain damage. You will need careful monitoring if this occurs and may need to be taken off tramadol.

Tramadol may also impair mental or physical abilities and affect your ability to drive a car. Avoid hazardous activities until you know how the drug affects you.

Tramadol interacts with many other medications, which can lead to life-threatening interactions including breathing problems, sedation, and coma. Your healthcare provider will weigh the pros and cons of your medication regimen and may consider changing your other prescriptions or closely monitoring you if you have to take tramadol.

Antidepressants and Anti-Anxiety Medications

Medications used to treat depression, anxiety, panic disorders, or insomnia can interact with tramadol and increase the risk of respiratory depression and/or serotonin syndrome. These drugs include:

• Benzodiazepines: It is not usually recommended to take tramadol with benzodiazepines—Xanax (alprazolam), Klonopin (clonazepam), Valium (diazepam), Ativan (lorazepam), Halcion (triazolam). This combination increases the risk of extreme sedation, respiratory depression, coma, and death. 
• Serotonin reuptake inhibitors (SSRIs): Antidepressants such as Prozac (fluoxetine) and Paxil (paroxetine) block CYP2D6, an enzyme that plays a role in metabolizing tramadol. This interaction increases blood concentrations of tramadol while also decreasing odesmethyltramadol (M1), reducing the drug's therapeutic effects. Tramadol dose may need to be adjusted and careful monitoring is needed. 
• Serotonin and norepinephrine reuptake inhibitors (SNRIs): Antidepressants that affect serotonin and norepinephrine, such as Cymbalta (duloxetine) or Effexor (venlafaxine), increase the risk of serotonin syndrome when taken with tramadol.
• Wellbutrin (bupropion): This medication used for depression or smoking cessation is a CYP2D6 inhibitor. Tramadol dose may need to be adjusted and you will need to be monitored carefully for adverse reactions, including respiratory distress and sedation, especially if stopping Wellbutrin.
• Other antidepressants: Tricyclic antidepressants (TCAs) and the antidepressants Remeron (mirtazapine) or Oleptro (trazodone) affect serotonin and increase the risk of serotonin syndrome. Careful monitoring for signs of serotonin syndrome is needed.

Central Nervous System (CNS) Depressants

Combining tramadol with CNS depressants increases the risk of extreme sedation, as well as dangerous slowing of the heart and breathing rate that can lead to coma and death. CNS depressants include:

• Alcohol
• Sedatives/hypnotics
• Anxiolytics
• Tranquilizers
• Muscle relaxants
• General anesthetics
• Antipsychotics
• Other opioids

Mixed agonist/antagonist and other partial agonist opioid analgesics, such as Sublocade (buprenorphine), butorphanol, nalbuphine, and pentazocine may reduce the analgesic effect of tramadol and lead to withdrawal symptoms.

Cardiovascular Medications

The effects of blood thinners and medications used for high blood pressure and heart conditions can be altered when taken with tramadol. These cardiovascular medications include:

• Coumadin (warfarin): In rare cases, the effects of this blood thinner may be altered, including clotting time. Monitoring is needed and dosages of warfarin or tramadol may need to be adjusted.
• Diuretics: Opioids can cause hormone release that reduces the effectiveness of diuretics. Monitoring of urine output and blood pressure is needed and the diuretic dose may need to be increased.
• Heart medications: Cardioquin (quinidine) used to treat arrhythmias (irregular heartbeats) is also a CYP2D6 inhibitor. Digitek (digoxin) toxicity (used to treat heart failure and arrhythmias) can occur when it is combined with tramadol. Digoxin or tramadol doses may need to be adjusted, and you will need to be monitored carefully for dangerous adverse reactions or toxicity.

Infection Medications

Drugs used to treat bacteria, fungal, or viral infections can interact with tramadol and you may need to be carefully monitored while on both medications.

• Macrolide antibiotics: Erythrocin (erythromycin) and other macrolide antibiotics block CYP3A4, an enzyme that helps metabolize tramadol, increasing blood levels of the drug. After stopping Erythrocin, tramadol concentration decreases. If you are on both medications you will need to be monitored closely for seizures, serotonin syndrome, and signs of respiratory depression. 
• Nizoral (ketoconazole): This antifungal medication also inhibits CYP3A4, increasing blood levels of tramadol. Careful monitoring is needed.
• Norvir (ritonavir): This protease inhibitor (PI) medication used to treat HIV also blocks CYP3A4, which increases blood levels of tramadol. Careful monitoring is needed.
• Rifadin (rifampin): This medication used for tuberculosis (TB) is also a CYP3A4 inducer that decreases blood concentrations of tramadol, making it less effective. Adding a CYP3A4 inducer while on tramadol may also cause withdrawal symptoms due to the reduction in potency.

Other Medications

There are many other types of drugs that can interact with tramadol, such as allergy medications, anti-seizure medications, and migraine medications. Some include:

• Anticholinergics: Using tramadol along with anticholinergic drugs, including first-generation antihistamines such as Benadryl (diphenhydramine) and Ditropan (oxybutynin) for overactive bladder, may increase the risk of urinary retention and/or severe constipation. Monitoring for urinary retention or lack of intestinal motility is needed.
• Anti-seizure medications: Tegretol (carbamazepine) and Dilantin (phenytoin) are CYP3A4 inducers that decrease blood concentrations of tramadol, making tramadol less effective. Tramadol can also increase the risk of seizures, potentially making these drugs less effective. If you stop taking the seizure medications, the blood concentration of tramadol will increase and raise the risk of dangerous side effects.
• Other serotonergic drugs: In addition to antidepressants, drugs that increase the risk of serotonin syndrome include triptans such as Maxalt (rizatriptan) used for migraines, 5-HT3 receptor antagonists (serotonin blockers) such as Aloxi (palonosetron injection) used to prevent nausea and vomiting during chemotherapy, and Anafranil (clomipramine) used to treat obsessive-compulsive disorder.

If taken with recreational or controlled substances, like alcohol, other narcotics, anesthetics, tranquilizers, and sedatives, tramadol can affect breathing and even cause it to stop.