Tramadol Drug Interactions & 5 Medications to Avoid 

Tramadol is a prescription painkiller in the opioid class. In 2021, doctors wrote about 30.5 million prescriptions for this drug in the United States.[1] Each prescription likely came with a list of instructions, including potential interactions. If you lost yours, you could be missing vital information that could save your life. 

Tramadol is powerful, and it’s even more dangerous when combined with common substances like opioids and benzodiazepines. Here’s what you need to know to stay safe. 

Negative Tramadol Interactions: Top Medications to Avoid 

Opioids like tramadol can sometimes be dangerous when taken alone. Very high doses can lead to respiratory suppression, and this can be fatal. 

Combining opioids with other substances can make them even more dangerous. Researchers warn that common drug/drug combinations are at least partially responsible for the high death rates associated with opioid overdose.[2]

It’s critical to talk with your doctor and pharmacist about your tramadol use and the other medications or substances you take. An open and frank discussion could help you avoid dangerous or even deadly combinations. 

These are the top five types of medications your team might wish to discuss with you while you’re taking tramadol. 

1. Serotonin Boosters 

Serotonin is a natural chemical that regulates behavior, mood, memory and gastrointestinal health. When levels are too low, people may develop mental health challenges, such as depression, obsessive-compulsive disorder or anxiety disorders.[3] 

Doctors consider serotonin-based therapies crucial in treating mental health challenges.[3] If you’re struggling with depression or anxiety, your doctor might recommend these medications in addition to therapy, physical exercise and other lifestyle changes. However, adding these medications to tramadol can be deadly. 

Tramadol can also boost serotonin levels.[1] Taking two medications with this function can lead to serotonin syndrome, which can be life-threatening. Symptoms include shaking, stiff muscles, agitation and delirium. In severe cases, people develop seizures.[3]

Common medications that boost serotonin include the following:[3,4]

• Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), olanzapine (Zyprexa) and paroxetine (Paxil) 
• Serotonin norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor)
• Tricyclic antidepressants, such as amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin) and clomipramine (Anafranil) 
• Triptans, such as almotriptan (Axert), eletriptan (Relpax) and frovatriptan (Frova) 
• Migraine medications, such as zolmitriptan (Zomig), rizatriptan (Maxalt) and sumatriptan (Sumavel) 
• Painkillers, like fentanyl (Duragesic), meperidine (Demerol) and methadone (Methadose)
• Illicit drugs, like methamphetamine and cocaine 
• Carbamazepine (Equetro)
• Cyclobenzaprine (Amrix)
• Dextromethorphan (Tussin Cough) 
• Lithium 
• Metoclopramide (Reglan) 
• Mirtazapine (Remeron) 
• Ondansetron (Zofran) 
• Phenelzine (Nardil)
• Selegiline (Zelapar) 
• St. John’s wort 
• Tranylcypromine 
• Trazodone 

2. Liver Metabolizers 

The liver is a critical organ that detoxifies the blood. Medications pass through the bloodstream and into the liver, where they’re metabolized and scrubbed from blood cells.[5] While the process is critical for all drugs, it’s especially important for people who take tramadol. 

The liver uses chemicals to break down each dose of tramadol you take. When your body doesn’t have enough of this chemical, the drug can build up within the bloodstream and lead to all sorts of health issues, including overdose.[6]

Medications that can alter liver function are called CYP3A4 and CYP2D6 inhibitors. Plenty of them exist, including the following:[7]

• Clarithromycin (Biaxin)
• Diltiazem (Cardizem)
• Erythromycin (Erymax, Tiloryth)
• Itraconazole (Sporanox) 
• Ketoconazole (Nizoral) 
• Nefazodone (Sezone)
• Ritonavir (Norvir)
• Telithromycin (Ketek) 
• Verapamil (Callan) 

3. Opioid Antagonists 

Opioid antagonists are medications that block drugs like tramadol from latching to opioid receptors throughout the brain and body. They can also kick active drugs from their connections, reversing an overdose in seconds.[8] These medications are commonly used to treat opioid use disorder (OUD). 

These medications can save someone’s life during an overdose. A quick spray of an opioid antagonist in the nose could help a person regain consciousness in seconds. These therapies can also offer protection during the early days of recovery. If someone relapses to opioid misuse, they won’t get high. 

Taking opioid agonists like naltrexone (Vivitrol) with tramadol can cause intense withdrawal symptoms, such as nausea, vomiting, muscle aches, headaches and chills. 

4. Diuretics 

Water makes up about 60% of an adult’s body weight. When you’re holding in too much fluid, painful swelling in the legs and hands can appear. Heart problems often cause this problem, as can liver disease. Diuretics can help the body remove excess fluids.[9]

Common diuretics include the following:[10]

• Furosemide (Lasix) 
• Torsemide (Demadex) 
• Bumetanide (Bumex) 
• Metolazone (Zytanix, Metoz) 
• Chlorthalidone (Thalitone)
• Hydrochlorothiazide (Microzide)
• Chlorothiazide (Diuril) 
• Spironolactone (CaroSpir) 
• Eplerenone (Inspira)

Taking these medications with tramadol can be dangerous. Researchers say tramadol can work directly on fluid regulation systems within the body, causing excess fluid release and low sodium levels within the body. Since tramadol also works on the serotonin system (which also works on the kidneys), the problem could worsen.[11]

Someone losing too many fluids is also flushing salt from the body. This can cause an issue called hyponatremia. Symptoms can include anorexia, nausea, vomiting, headache and fatigue. Without treatment, problems can worsen. Seizures and coma can develop.[12] Anyone showing these symptoms should see a doctor right away, as it’s a medical emergency. 

5. Sedatives 

Sedating drugs slow your heartbeat, breathing rates and brain activity. Tramadol is a sedative, as are many other common prescription and street drugs. 

People who combine opioids (like tramadol) with sedating drugs (like sedative-hypnotic prescription drugs) have a six times higher overdose risk when compared to people who use opioids alone.[13]

Common sedatives that shouldn’t be used with tramadol include the following:[13]

• Benzodiazepines, such as alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium), midazolam (Versed), clonazepam (Klonopin), triazolam (Halcion) and chlordiazepoxide (Librium)
• Sleep medications, such as temazepam (Restoril), zaleplon (Sonata), zolpidem (Ambien) and eszopiclone (Lunesta) 
• Barbiturates, such as amobarbital (Tuinal), butalbital (Esgic, Fiortal), pentobarbital (Nembutal), secobarbital (Seconal), primidone (Mysoline) and phenobarbital (Luminal) 
• Muscle relaxers, such as tizanidine (Zanaflex) and cyclobenzaprine (Amrix)
• Diphenhydramine (Benadryl) 
• Opioids, such as oxycodone (Xtampza and Roxicodone), codeine (Maxiflu, Calcidrine), hydrocodone (Vicodin and Lortab) and fentanyl (Actiq and Duragesic) 
• Alcohol 

Any sedating medication can make you feel sleepy and slow. Combining this type of medication with tramadol can lead to more significant symptoms, such as the following:[13]

• Drowsiness
• Dizziness or lightheadedness
• Confusion and impaired cognitive function
• Respiratory depression
• Decreased motor coordination
• Coma

Without quick treatment, these episodes can be fatal. Anyone using tramadol that seems too sedated or nonresponsive needs your help. Call 911 and tell the operator about the symptoms you see. Follow the directions you’re given and stay with the person until help arrives. 

If you’re uncertain if someone has overdosed, always err on the side of caution and call for help. If you have naloxone on hand, administer it.

Getting Help for Tramadol Addiction 

Working with your doctor and pharmacist can help you avoid interactions when you have a valid tramadol prescription. If you’re misusing the drug, your risks are even higher. You may not have anyone watching your prescription use and helping you to stay safe. It’s critical to get help. 

Tramadol addiction, and opioid use disorder, are treatable with Medication for Addiction Treatment (MAT) programs. Doctors use prescriptions like Suboxone to address tramadol-induced brain cell damage. When you’re enrolled in MAT, you may have fewer opioid withdrawal symptoms and cravings. Stopping opioid misuse this way is much easier than trying a cold-turkey approach. 

Bicycle Health administers MAT via telemedicine. You’ll work with a skilled, trained and compassionate team that has decades of experience in helping people recover from OUD. 

You’ll get the prescription you need filled at a pharmacy near you, but all of your appointments will take place via your computer or phone. This makes the entire process convenient, private and manageable. No matter where you live, treatment is accessible. 

Contact us to find out if this model of treatment is right for you. We can often get you a same-day prescription for Suboxone, so you can get started on your recovery from tramadol misuse right away.