Nucynta vs Tramadol: drug comparison guide

Nucynta vs Tramadol: drug comparison guide
November 18, 2015 9:48 PM

Nucynta (Tapentadol) and Tramadol (Ultram) are pain killing medications. This article features a detailed comparison of medical uses, mechanism of action, side effects and precautions of both drugs. You will also learn about intake methods and other important facts concerning these pain killers.


The scientific name for nucynta is tapentadol. It is a centrally acting opoid analgesic belonging to the benzenoid class and has a dual mode of action as an agonist. It also acts as a norepinephrine reuptake inhibitor. The analgesic properties of the drug are seen within thirty two minutes of administration and last for about 4 to 6 hours (1).

The dual action of this drug is quite similar to tramadol which is its ability to reuptake the opoid receptor and stop the reuptake of norepinephrine. This drug has weak effects on the reuptake of serotonin and is quite a potent opoid which has no active metabolites.  The potential of this drug lies somewhere between morphine and tramadol and its analgesic efficacy is like that of oxycodone despite its lower side effects.

This drug was approved by the FDA (in November 2008), MHRA of UK (4th February 2011) and by the TGA of Australia (24th December 2010).


Nucynta was first made by Grunenthal in a joint effort with Johnson and Johnson Pharmaceutical Research and Development. This drug is being marketed in the immediate release form in the form of oral tablets of 50 mg, 75 mg and 100 mg; it is also present in extended form in the form of oral release tablets of 50 mg, 100 mg, 150 mg and 250 mg under the brand name Nucynta ER.

Nucynta is the first drug in the centrally analgesic class which has been approved in more than 25 years. The status of this drug is at various stages of development at this time.

Medical Uses of Nucynta

The nucynta tablets are usually prescribed for the treatment of moderate to severe pain. The severe pain here means that a pain which is caused due to some affective cause and goes away as soon as the cause of the pain is healed. Neuropathic pain can also be relieved by taking nucynta extended released tablets (2).

This medicine can also be used by diabetic patients to treat pain. The nucynta extended released tablets are only used by those patients who take the medicines throughout the day to relieve the pains which can’t be healed by other medications and drugs. Nucynta belongs to the class of tablets which are known as opiate analgesics. It functions by changing the way the brain and the nervous system respond to pain.

A study was recently published which said that other treatments for pain treatment are also available but patients need more serious therapies and medications to relieve pain appropriately. Experts are of the view that nucynta is quite beneficial for treating pain.

Paul Chang who is the Vice President of internal medicine at Jassen Pharmaceuticals says: “Different clinical trials have shown that nucynta is quite beneficial for treating moderate to severe pain. We are happy that FDA has approved this drug because it is an important and newer options for patients to treat chronic pain.” (3, 4, 5)

A clinical of nucynta was done recently in which the Johnson and Johnson Pharmaceutical Research and Development conducted a double blind, randomized, active placebo phase 3 investigation. The researchers also evaluated the safety of the drug over 1,100 participants from moderate to severe pain over a time period of 12 months. The researchers found out that Nucynta is both safe and effective.

Experts have the view that nucynta is quite safe for treating moderate to severe pain but experts also believe that it is essential to develop a strong educational program about the safe and responsible use of this drug to avoid its inappropriate use (6).

Dosage and intake methods

Nucynta is available in different dosage strengths. It is present in 50 mg tablets, 100 mg tablets, 150 mg tablets, 200 mg tablets and 250 mg tablets.

The main thing to note is that this medication is an opioid drug and dosing for this drug depends upon the individual needs of each person. The following things are to be noted while administering Nucynta:

  • The patient’s degree of tolerance to opioid drugs
  • The medical status and general condition of the patient
  • The type and severity of the pain
  • Risk factors of drug abuse or diversion and a history of addiction, abuse or diversion.

The general starting dose of this drug is about 50 mg, 75 mg and 100 mg to be taken every 4 to 6 hours upon the sensation of severe pain (7).

When you are taking the medication on the first day then the second dose should be taken exactly one hour after the first dose if you don’t feel relief after the first medication. The subsequent dosing of the drug is about 50 mg, 75 mg or 100 mg to be taken every 4 to 6 hours to maintain analgesia.

Doses greater than 700 mg on the first day followed by subsequent doses of 600 mg daily aren’t recommended.

The following is the exact dosage of the drug according to the specific problem:

  • Renal impairment: there isn’t any specific dosage recommended for renal impairment.
  • Hepatic impairment: the initial dosage for hepatic treatment is about 50 mg to be taken no more than once every 8 hours.
  • Elderly patients: the recommended dosage for elderly patients for renal and hepatic function is the same as the doses for younger people with renal and hepatic impairment. It is recommended that the starting dose of the drug should be lower because the elderly patients usually have decreased renal and hepatic functioning.

Intake methods

This tablet comes in two forms which are normal tablets and extended release tablets. Both these intake methods have been mentioned below:

1. Tablets

The nucynta tablets need to be taken through the mouth every 4 to 6 hours as needed. Your doctor may instruct you to take a second dose after the first dose to treat pain more effectively. You can take the tablets with or without food. People who have nausea should take the drug with food. You should also ask your health care provider about other ways to treat nausea.

2. Extended release tablets

You should swallow the extended release tablets one by one with plenty of water. Swallow each tablet carefully right after you put it in your mouth. You shouldn’t leave the medicine without consulting with your doctor. You may experience withdrawal symptoms if you leave the medicine suddenly. Some common withdrawal symptoms include anxiety, irritability, restlessness, yawning, difficulty falling asleep, shivering and uncontrollable shaking of the body.

Mechanism of action

Most manufacturers of nucynta currently list the mechanism of this drug currently as unknown but they state that it is likely a combination of agonistic effect at the mu-opioid receptor and the inhibition of nor-epinephrine uptake. Nucynta is a drug of sigma-2 receptor agonist. But it hasn’t been determined so far that whether or not the sigma activity contributes to the nucynta analgesic effects.

Pharmacokinetics – actions after intake

The following steps take place after the intake of nucynta:

1. Absorption

The mean bioavailability after a single dose of nucynta is about 32% because of extensive first-pass metabolism. The maximum serum concentrations of nucynta are found after around 1.25 hours of dosage. The dose proportional increase to Cmax and the AUC values of nucynta have been seen after 50 to 150 mg dosage range.

A multiple dose study was recently done with doses of 75 to 175 mg. The study showed a mean accumulation factor of 1.6 for the parent drug and about 1.8 for major nucynta-O-glucuronide which are mainly determined by the dosing interval and the half-life of the drug and its metabolism.

2. Distribution

Nucynta is distributed widely through the body. The volume of distribution of nucynta is about 540+/-98 L after the internal administration. The protein binding of plasma is quite low and counts up to about 20%.

3. Metabolism and elimination

The metabolism of nucynta in humans is quite extensive. Almost 97% of parent compound passes through the process of metabolism. Nucynta is metabolized through phase 2 pathways; only a small amount is metabolized through phase I oxidative pathways.

The main pathway of the metabolism of nucynta is the conjugation with glucuronic acid to produce glucuronides. About 70% of the dose is excreted in the urine in conjugated form after the oral administration.

About 3% of the drug is excreted through the urine as unchanged drug. Nucynta is metabolized to N-desmethyl nucynta by CY2CP9 and CYP2C19 and into hydroxyl nucynta by CYP2D6 and is further metabolized through conjugation. Thus the drug metabolism which is mediated through cytochrome P450 system has less importance than phase 2 conjugation.

Nucynta and its metabolites are excreted through the kidneys. The terminal half-life after oral administration is about 4 hours. The total clearance is about 1530 +/- 177 ml/min.


Nucynta overdose can prove to be quite dangerous. The exact symptoms of the overdose depend upon how much the drug was taken and other possible factors which include irregular breathing, coma and even death at times. One treatment can be pumping the stomach if the overdose is recent. Antitoxins can also be used but when heart and breathing problems occur.

The experiences with nucynta overdose is quite limited because it is a new medicine. Some possible symptoms of nucynta overdose include:

  • Blue skin
  • Drowsiness
  • Coma
  • Low blood pressure
  • Cardiac arrest
  • Loss of life
  • Limp muscles
  • Cold

The effects of nucynta overdose can be fatal but antidotes can be taken to counteract some of the side effects. The antidote should only be given if heart or breathing problems occur and should be given at reduced dosages and used quite cautiously. Your health care provider may use the technique of ‘pumping the stomach’ if the overdose was recent.

Some treatment options for nucynta overdose include supportive care in which the symptoms of overdose are treated. A person may need to have breathing tube inserted if the breathing becomes dangerously low.

Side effects

Some major side effects of nucynta overdose include dizziness, drowsiness, constipation, nausea and vomiting. You should inform your pharmacist right away if any of these symptoms worsen.

You should eat a diet with appropriate fiber to prevent constipation and drink plenty of water and have exercise. You should consult your pharmacist for help in selecting a laxative. You should get up slowly when rising from a sitting position to reduce the risk of dizziness and light headedness.

You should remember that the doctor has prescribed the medication for you because he thinks that its benefits are greater than its side effects. Most of the people who use this medicine don’t suffer from any side effects.

You should inform your doctor right away if you suffer from any serious symptoms like abdominal pain, confusion and difficulty urinating. You should also get medical help right away if you suffer from any serious side effects like fainting, seizures, drowsiness and shallow breathing.

Nucynta can sometimes increases the serotonin levels and can cause quite a serious health condition known as serotonin syndrome. The risk increases especially if you are taking the drugs which increase the serotonin levels. So you should inform your doctor about the drugs you intake. You should also get medical help if you suffer from symptoms like loss of coordination, hallucinations, vomiting, diarrhea, severe dizziness, unusual restlessness and muscle twitching.

Sometimes an allergic reaction can also be caused due to this drug but it is quite rare. But you should get medical help if you notice the symptoms of a serious allergic reaction like swelling, rash, trouble breathing and severe dizziness.

You should remember that the side effects mentioned here aren’t complete. You should consult your doctor or pharmacist if you notice some other side effects.

You should call the doctor immediately to get medical advice about your condition. People living in the US can report their side effects to FDA at 1-800-FDA-1088 and people living in Canada should report the side effects at 1-866-234-2345.

Decreased efficiency causes

The following things reduce the efficiency of nucynta:

  • The efficiency of nucynta is reduced when it interacts with other drugs. About 734 drugs in total are known to react with nucynta. Some common drugs which can interact with nucynta include ambien, lyrica, Nexium, vitamin D3, xanax, tramadol and Celebrex.
  • You shouldn’t take nucynta if you suffer from severe dizziness, increased pressure in brain, a history of seizures or growth in the brain.


Tramadol is an opioid medication which is used to treat from moderate to severe pain. The onset pain relief occurs after about one hour when the drug is taken as an immediate-release formulation. There are two different mechanisms involved. First it is bound to u-opioid receptor. Secondly it stops the reuptake of serotonin and norepinephrine (9).

Some serious side effects of the drug intake include seizures, decreased alertness, drug addiction and increased risk of serotonin syndrome. Some common side effects include nausea, itching, constipation and others. A change in dose is usually recommended in people with kidney and liver problems. This drug isn’t recommended in breast feeding women and those with increased risk of suicide.

Tramadol is sold in the market as a racemic mixture of both R- and S-stereoisomers. The reason is that these two isomers complement one another’s analgesic activity. This drug is often combined with paracetamol because it can improve the efficiency of tramadol in relieving pain. Tramadol is passed through metabolism and is converted to O-desmethyltramadol which is a potent opioid. It belongs to the benzenoid class.

Tramadol was first launched in 1977 and marketed as Tramal by the German pharmaceutical company Grunenthal GmbH in West Germany. It was launched in other countries like US, UK and Australia 20 years later.

Medical uses

Tramadol is recommended for the treatment of mild to severe pain both chronic and acute. This drug is usually recommended for the treatment of pain in fibromyalgia by the European League against Rheumatism (9). The analgesic effects take about one hour to complete their effect and reach their peak levels in 2 to 4 hours after the oral administration with immediate release formulation. Tramadol has about one-tenth the potency of morphine and is quite potent when compared to codeine and pethidine.

The effectiveness of the drug is just like morphine for a moderate pain but it is less effective than morphine in case of severe pain. The pain killing effects reach their peak levels after 3 hours and last for about 6 hours.

The analgesic effects are reversed by naloxone which indicates that its opioid action isn’t the sole contributing factor. The analgesic effects of tramadol are also reversed by alpha adrenergic receptor antagonist like tapentadol in the sense that it doesn’t only binds itself with the mu opioid receptor but it also stops the reuptake of norepinephrine and serotonin because of its action on the serotonergic and noradrenergic systems such as the ‘atypical’ opioid activity. The available doses of this drug include tablets, capsules, injections and extended release formulations.

Dosage and intake methods

The dosage is from mild to moderate severe chronic pain which doesn’t has the rapid onset of analgesic effect. The initial dose for this drug is 25 mg every morning. There should be 25 mg increment as separate doses every 3 days to reach 100 mg per day to be taken 25 mg 4 times a day. The daily dose should be increased to 50 mg after every 3 days to reach 200 mg to be taken as 50 mg to be taken 4 times a day. The tramadol 50 to 100 mg can be administered for pain relief every 4 to 6 hours and it shouldn’t exceed more than 400 mg per day (10).

Now let us see the management of moderate to severe chronic pain in adults who require round the clock treatment for their pain for an extended period of time. The initial dose of the extended release tablets should be 100 mg once daily and should be titrated as necessary up to 100 mg increase after every 5 days for relieving pain and depending upon tolerability. The maximum dose of the extended release tablets is 300 mg per day and the dose shouldn’t exceed than this.

Now let us see the dosage for patients in whom the rapid onset of analgesic effect is required and for whom the benefits of the drug overweigh the risk of discontinuation. The dose is about 50 to 100 mg to be administered as needed for relieving pain every 4 to 6 hours and shouldn’t exceed more than 400 mg daily.

Intake methods

Tramadol comes in the form of a tablet, an extended release tablet, an extended release capsule and orally disintegrating tablet to be taken through the mouth. The regular and the orally integrated tablet should be taken with or without food every 4 to 6 hours as needed.

The extended release tablet and the extended release capsule should be taken once daily. You should take the extended-release tablet and the extended-release capsule at the same time every day. You can take the tablet with or without food if you are taking the extended-release capsule. You can either always take it with food or without food if you are taking the extended-release tablet.

You should take the tablet exactly as directed by the doctor. Don’t take more than a single dose of the medicine or take more than that prescribed by the doctor. Serious side effects are caused if you take the medicine more than the recommended dosage.

Your doctor will start on low dose and gradually increase the dosage and it wouldn’t be more than every 3 days if you are taking regular or orally disintegrating tablets or every 5 days if you are taking the tablets in the extended release capsules. The intake methods of extended release tablets and orally disintegrating tablets has been mentioned below:

Extended release tablets

You should swallow the extended release tablets and the extended release capsules whole. You shouldn’t split, chew or crush the tablets.

Orally disintegrating tablets

Peel back the foil to remove the tablet from the blister pack. Don’t push the tablet through the foil. Now put the tablet in your mouth and it will dissolve in few seconds. You can take the tablet with or without food. Don’t crush, chew or split the tablet.

Mechanism of action

Tramadol acts as u-opioid receptor agonist, releasing agent, norepinephrine reuptake inhibitor, NDMA receptor antagonist, nicotine receptor antagonist, TRPV1 receptor antagonist and M1 and M3 muscarinic acetylcholine receptor antagonist.

Tramadol shows inhibitory action on the 5-HT2c receptor. The antagonism of 5-HT2c is responsible to some extent for the reducing effect of tramadol on obsessive and depressive compulsive symptoms in patients having pain and neurological illnesses. 5-HT2c blockade is also responsible for lowering the seizure threshold because 5-HT2c knockout in mice displays increased vulnerability to epileptic seizures with can sometimes result in spontaneous death.

But the reduction of the seizure threshold can be attributed to the inhibition of the GABA receptors at high doses. Also the tramadol’s active metabolite O-demethyltramadol is a high-affinity ligand of the k-opioid receptors and it could be involved in the development of seizures in some individuals.

Actions after intake – pharmacokinetics

The following steps are involved in the pharmacokinetics of tramadol:

1. Absorption

Tramadol is rapidly and completely absorbed after oral administration. The availability of 100 mg oral dose is about 75%. The peak plasma concentration of tramadol occurs at two and three hours after the administration in healthy adults. Both enantiomers of tramadol and M1 follow a parallel time course in the body following the single and multiple doses. The steady state plasma concentrations of tramadol and M1 are obtained within two days of dosing. Currently there is no evidence of self-induction.

2. Distribution

The volume of tramadol in male and female subjects was 2.6 and 2.9 L/kg after the oral administration of 100 mg dose. The binding dose in the human plasma proteins is about 20% and the binding is independent of the concentration up to 10 ug/mL.

3. Metabolism

Tramadol is extensively metabolized by a number of mechanisms after the oral administration. These methods include CYP2D6 and CYP3A4 and also the conjugation of the parent and the metabolites. About 30% of the dose is passed unchanged through the urine and 60% is excreted as metabolites. The main metabolite pathway is N- and O-demethylation and glucuronidation in the liver. The metabolite M1 is quite active in animal models.

4. Elimination

Tramadol is eliminated from body through the metabolism of the liver and the metabolites are mainly excreted through the kidneys. The terminal plasma elimination half-lives of tramadol and racemic M1 are 6.3+-1.4 and 7.4+-1.4 hours respectively. The plasma elimination half-life of tramadol increases from six to seven hours when multiple doses are given.


Tramadol overdose happens when a person intakes more than the recommended intake of the drug. Some common signs and symptoms of tramadol overdose are mentioned below:

  • Respiratory depression
  • Hypotension
  • Rare death due to abuse and misuse of the drug
  • Cardiac arrest
  • Seizures
  • Constricted pupils

Overdosage from tramadol can be potentially lethal and a person should immediately contact his healthcare provider for assistance. A proper attention should be given to maintain ventilation and supportive care. Some supportive measures should be taken to manage pulmonary edema and circulatory shock.

The use of naxolone can also reverse the overdose symptoms but the problem is that the risks of seizures are also increased with the administration of the drug. Seizures need to be controlled with diazepam.

Side effects

Some major side effects of tramadol include dizziness, drowsiness, lightheadedness, nausea, vomiting and constipation. Some of the side effects might decrease after you keep on taking the medication for some time. You should immediately inform the doctor if any of the symptoms worsen after the intake of the drug.

You should drink plenty of water, exercise regularly and eat a fiber rich diet in order to prevent constipation. You should consult your pharmacist in selecting the right laxative. You should get up slowly from a lying to reduce the effect of dizziness.

You should also inform the doctor if any of the following rare but serious side effects occur:

  • Seizure
  • Slow breathing
  • Fainting
  • Difficulty getting up
  • Drowsiness

Reduced efficiency causes

The following things reduce the efficiency of tramadol:

  • The efficiency of tramadol is reduced when it is consumed with other drugs. A total of 735 different drugs are known to interact with tramadol. Some common medications which can interact with tramadol include Norco, Nexium, xanax, vitamin C, Celebrex, fish oil, Lipitor and aspirin.
  • The efficiency of tramadol is also reduced when it is taken by allergic people and they can’t get full benefit from the medication.

Clinical trials of Nucynta vs Tramadol

There is one study which exclusively gives a comparison between nucynta and tramadol. This study has been mentioned below:

The main objective of the study was to review the pharmacokinetics, pharmacodynamics and clinical efficacy of nucynta and then compare it with tramadol which is the first kind of drug in this class (11).

The data for the study was collected from Medline/PUBMED and EMBASE searches. Many abstract meetings from multiple pain specialty were also searched.

The data results showed that oral nucynta is the second mu-opioid receptor and mono amine reuptake inhibitor which has been approved by the Food and Drug Administration. The drug was effective in a variety of pain states in both humans and animals. The drug behaved in a similar fashion to morphine. Oral nucynta should be administered in doses of 50 to 100 mg every four to six hours.

The researchers concluded in the research that nucynta is a better drug than tramadol. They said that nucynta has overcome some of the short comings of tramadol. It is more beneficial than tramadol in relieving pain.


The results of the above study clearly show that nucynta is a better drug than tramadol. The reason behind this is that nucynta has a better effect in relieving pain than tramadol. Some discrepancies and side effects of tramadol have been overcome by nucynta.

However you should know that only your doctor may prescribe you your medicine and it is up to him to select between tramadol and nucynta. This post does not replace proper medical advice.

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Written by: Michal Vilímovský (EN)
Education: Medical student, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
Article resources: See numbered references within the article
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Published: November 18, 2015 9:48 PM
Next scheduled update: November 18, 2017 9:48 PM
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