Two powerful pain options

Tramadol and hydrocodone/acetaminophen (Vicodin) are powerful pain relievers that can be prescribed when over-the-counter medications don’t provide sufficient relief. They’re often prescribed for short-term use following medical procedures or injuries.

Read on to find out how they work, how they compare, and why you should take them with caution.

Tramadol has two different actions in the body. It’s an opioid analgesic, which means that it attaches to receptors in your brain to change your perception of pain. It also works like an antidepressant, prolonging the actions of norepinephrine and serotonin in the brain.

Tramadol is available under several brand names, including ConZip and Ultram. Another medication, Ultracet, is a combination of tramadol and acetaminophen.

Vicodin is a brand-name drug containing hydrocodone and acetaminophen. Hydrocodone is an opioid analgesic. Acetaminophen is an analgesic (pain reliever) and an antipyretic (fever reducer). There are many generic brands of hydrocodone and acetaminophen too.

Due to the potential for overdose and misuse, in 2014 all hydrocodone products were moved to a new category by the U.S. Food and Drug Administration (FDA). They now require a written prescription, which you must obtain from your doctor and take to a pharmacy.

Tramadol is also considered a controlled substance. Prescriptions can be called to pharmacies, but many health systems are now adopting more stringent guidelines on prescribing this drug.

Both of these drugs can affect your driving, since they make you drowsy. Don’t drive or operate machinery while taking them, until you know how you react to them.

How they work

Analgesics change the way your brain perceives pain. Opioid analgesics, otherwise known as narcotics, are powerful medications. Tramadol also acts like an antidepressant, prolonging the action of neurotransmitters associated with mood. Both of these drugs are very effective in treating pain, but they can also be highly habit forming.

Who they’re for

Tramadol and hydrocodone/acetaminophen are prescription-strength pain relievers. Either of these medications may be prescribed following surgery or injury. They’re also useful for treating pain associated with cancer and other chronic illnesses such as arthritis. Hydrocodone/acetaminophen can also help reduce fever.

How they’re supplied

Tramadol is available in a variety of forms, including:

  • immediate release tablets, in 50 milligram (mg) strengths
  • extended-release tablets and capsules, available in 100 mg, 150 mg, 200 mg, and 300 mg strengths

Hydrocodone/acetaminophen is also available in many forms and strengths. Some of them are:


All hydrocodone/acetaminophen tablets now have limited amounts of acetaminophen in them. Too much acetaminophen can lead to liver damage.

Strengths available range from 2.5 mg to 10 mg hydrocodone, and 300 mg to 325 mg acetaminophen.

Oral solutions

These have also been reformulated to reduce the amount of acetaminophen in them. Strengths now available range from 7.5 mg hydrocodone/325 mg acetaminophen per 15 milliliters (mL) to 10 mg hydrocodone/325 mg per 15 mL.

How to take them

Based on the nature and severity of your pain, and other factors, your doctor will decide on the initial dose. They may start with the lowest possible dose to minimize side effects. The dose can then be adjusted as needed.

Don’t take extra acetaminophen with hydrocodone/acetaminophen medication. Excess acetaminophen can increase the risk to your liver, and will offer little additional pain relief.

You may have to take the medication several times a day at regular intervals. The medications work better if they are taken before the pain gets unbearable.

If you’re taking an extended-release capsule, be careful not to chew, split, or dissolve it. Usually, the extended-release capsule is taken once a day.

Common side effects of tramadol include:

Most of these side effects will resolve within a few days.

More serious side effects of tramadol can include:

  • seizures
  • mood problems (there is an increased risk of suicide in people with depression who take tramadol)
  • hypersensitivity reaction, including swelling of the tongue or throat, trouble breathing, and skin rash

Get immediate medical attention or call 911 if you experience these symptoms.

Common side effects of hydrocodone/acetaminophen can include:

  • dizziness
  • drowsiness
  • itching
  • constipation
  • loss of appetite
  • nausea and vomiting

Most of these side effects will lessen with time.

Serious side effects of hydrocodone/acetaminophen can include:

Get immediate medical attention or call 911 if you experience these symptoms.

Hydrocodone comes with a black box warning about the potential for misuse of this drug. The FDA requires a black box warning for drugs with associated serious or life-threatening risks.

Side effects of both drugs are more likely or can be more intense if you are older or have kidney or liver disease, chronic obstructive pulmonary disease, or other chronic disease.

The following adverse effects are possible with both tramadol and hydrocodone/acetaminophen. If you develop swelling of the tongue or throat, you may be having an allergic reaction to the medication. Opioids should be used with caution if you have:

Opioids can make it hard to urinate, especially for men who have benign prostatic hyperplasia (BPH).

Tell your doctor if you’re pregnant or nursing. These medications may be harmful to your developing baby and may pass through your breast milk.

You may experience mood changes, confusion, or hallucinations. Other serious complications include seizures, rapid heartbeat, and shallow breathing. If you have any of these symptoms, seek immediate medical help. Opioid overdose can slow your breathing rate and ultimately lead to coma or death.

Careful monitoring is recommended if you have cardiovascular disease or hypovolemia (a decrease in blood volume).

Black box warning

Hydrocodone/acetaminophen has a black box warning about the dangers of acetaminophen, especially at high doses. Acetaminophen is associated with acute liver failure. Tell your doctor if you’ve had liver disease.

When taking hydrocodone/acetaminophen, be sure to check the labels of other drugs that may also contain acetaminophen. Acetaminophen is also linked to rare, but potentially fatal, skin reactions. See your doctor immediately if you develop skin blisters or rash.

Tolerance and dependence

If you take either of these drugs for a long time, you may develop a tolerance to them. This means you’ll need a higher dose to achieve the same pain relief. These medications should be taken with great care because they can become habit-forming.

If you become dependent on opioids, you may have symptoms of withdrawal when you stop. Your doctor can help you taper off the drug slowly, which can help prevent withdrawal. You’re more likely to become dependent if you have a prior history of substance misuse.


Be sure to tell your doctor about all medications and supplements you use. Some may have dangerous interactions.

Tramadol has several drug interactions. Tell your doctor about all drugs and supplements you take, before you start taking tramadol.

These drugs should not be taken with tramadol:

These are some of the drugs that interact with tramadol, but you may still be able to take them together. Talk to your doctor if you are taking any of these drugs:

  • antibiotics, including erythromycin (E.E.S.), clarithromycin (Biaxin), and related drugs
  • anticholinergic drugs (antihistamines, drugs for urinary spasms and other drugs)
  • digoxin (Lanoxin)
  • other opioids
  • MAO inhibitors
  • quinidine
  • St. John’s wort
  • certain antidepressants
  • some antifungals
  • some HIV drugs
  • muscle relaxants
  • sleeping pills
  • triptans (used to treat migraine headaches)
  • anxiety and psychiatric medications
  • warfarin (Coumadin)

Hydrocodone/acetaminophen has several drug interactions. Tell your doctor about all drugs and supplements you take, before you start taking the medication.

These drugs shouldn’t be taken with hydrocodone/acetaminophen:

  • alcohol
  • azelastine
  • buprenorphine
  • butorphanol
  • conivaptan (Vaprisol)
  • eluxadoline
  • idelalisib (Zydelig)
  • orphenadrine
  • thalidomide

These are some of the drugs that interact with hydrocodone/acetaminophen, but you may still be able to take them together. Talk to your doctor before taking hydrocodone/acetaminophen if you are taking any of these drugs:

  • antidepressants
  • antihistamines
  • CNS depressants
  • CNS stimulants
  • magnesium sulfate
  • other opioids
  • seizure medications
  • sleeping pills and sedatives
  • sodium oxybate
  • warfarin

Don’t drink alcohol when taking opioids. Other medications that cause sleepiness, including cough or cold formulas, may contain ingredients that interact with opioids or increase the risk of sedation. Tell your doctor and pharmacist about all the medicines you’re currently taking.

Both of these drugs are available by prescription only, so your doctor will recommend one based on your symptoms and overall medical condition. If you have pain with fever, hydrocodone/acetaminophen is the more likely choice.

It’s important that you tell your doctor about underlying medical conditions and any other medications you use.