Tramadol vs Percocet

What is Tramadol? What is Tramadol used for?

Tramadol is a Generic name for an opioid pain reliever drug that is used for the treatment of moderate to moderately severe acute and chronic pain.  It works by changing the way brain responds to pain.

This drug may also increase levels of the neurotransmitters serotonin and norepinephrine. Tramadol is used to treat postoperative, dental, acute musculoskeletal and cancer pain. It is also often used as an adjuvant to NSAID therapy in patients with osteoarthritis. According to European League Against Rheumatism, it is recommended for the treatment of chronic pain caused by medical condition called fibromyalgia.

Recent study suggested that giving tramadol to patients before surgery may be very helpful to ease post-anesthesia shivering – a complication that usually develops in patients recovering from general anesthesia. Tramadol is available on the market in following dosage forms: tablet, tablet extended release, capsule extended release, suspension and disintegrating tablet.

Tramadol tablets are available in 50 mg and 100 mg and they are usually taken several times a day. Extended release tablets are available in doses of 100 mg, 150 mg, 200 mg, and 300 mg. Common Brand names for medications containing tramadol are: Ultram, Ultram ER, Rybix ODT, ConZip and Ryzolt.

Ultracet is Brand name for a medicine that contains a combination of tramadol and acetaminophen.   FDA approved tramadol in 1995. It is originally manufactured by the drug company Janssen Pharmaceuticals under the brand name Ultram.

What is Percocet? What is Percocet used for?

Percocet is a Brand name for a medicine containing a combination of two active ingredients: oxycodone and acetaminophen. Oxycodone is an opioid (narcotic) pain reliever drug that works by changing the feeling of pain perception in the brain. Acetaminophen is a less potent pain reliever and fever reducer drug that according to some studies may enhance oxycodone effects.

It is also added in many pain reliever products to reduce the dose of major analgesic, thus minimizing the risk of opioid drugs side effects, for the same efficacy.

Percocet is used to treat moderate to severe acute or chronic pain. It is available in tablet form in next dosage combinations: 2.5/325 mg, 5/325 mg, 7.5/325 mg and 10/325 mg. The FDA approved the combination of oxycodone and acetaminophen in 1980. It is manufactured by Endo International plc, formerly Endo Pharmaceuticals. Other Brand names on the market with same combinations Ratio – Oxycocet and Endocet.

What is the difference between Tramadol and Percocet in their mechanism of action?

Tramadol has two different mode of action. First, tramadol can bind to μ-opioid receptors causing inhibition of ascending pathways responsible for pain in CNS, and secondly, tramadol can inhibit reuptake of serotonin and norepinephrine. Tramadol may cause the reduction of the seizure threshold due to its inhibitory effects on the serotonins 5-HT2C receptors.

However, the seizure threshold reduction may be also attributed due tramadol’s antagonism of GABA receptors in CNS when it is taken in higher doses. In addition, this drug’s active metabolite known as O-desmethyltramadol has a high affinity to the δ-opioid receptors in the CNS, and by binding to these receptors it may provoke seizures in some individuals, because δ-opioid receptor agonists are known as seizure inducers.

Oxycodone which is the main active ingredient in Percocet, works as a weak agonist of mu, kappa, and delta opioid receptors in the CNS. Oxycodone primarily binds to opioid mu-type receptors that are coupled with G-protein receptors. It works as positive or negative modulator of synaptic transmission via G-proteins that in last step activate effector proteins.

When oxycodone binds to its receptors it stimulates the switching of GTP for GDP on the G-protein complex.  Oxycodone lowers cAMP intracellular levels by inhibiting enzyme adenylate cyclase. Furthermore, oxycodone may inhibit effects of pain transmission neurotransmitters such as dopamine, GABA, substance P, acetylcholine, and noradrenaline.

Oxycodone can also inhibit release of hormones such as: vasopressin, somatostatin, insulin and glucagon.  By activating kappa-receptor this drug closes N-type voltage-operated calcium channels and by activating mu and delta receptors it opens calcium-dependent potassium channels. This result is hyperpolarization of neural membrane and further reduces of neuronal excitability.

Acetaminophen from Percocet is a selective COX-2 enzyme inhibitor that works by inhibiting synthesis of prostaglandins responsible for pain. Acetaminophen’s analgesic actions involve mostly peripheral influences, but it can also inhibit COX-2 enzym in the brain.  This drugmay also inhibit enzyme prostaglandin synthetase.

Antipyretic activity of acetaminophen is mediated through hypothalamic heat regulating centers. After metabolism, acetaminophen produce reactive metabolite chemically known as N-acetyl-p-benzoquinone imine (NAPQI) that can cause in high amounts and in predisposed patients a very dangerous and potentially fatal, liver necrosis through processes of lipid peroxidation. That why acetaminophen should never be taken in amounts than 4 g daily.

Differences and similarities between Tramadol and Percocet

tramadol vs oxycodone

Tramadol and Percocet are prescription drugs that are used to treat moderate to severe pain.  They belong to the therapy class of drugs known as opioid analgesics or narcotics which work in the brain to change how body feels and responds to pain.

Because these drugs are narcotic, they have a high potential for abuse and are classified as Schedule II list of drugs. Both drugs may cause physical and mental dependency if they are abused, and also severe withdrawal effects.

Chemically these drugs are different.  Tramadol belongs to the class of organic compounds known as anisoles containing a methoxybenzene in its structure. Oxycodone belongs to the class of organic compounds known as morphinans. Also, Percocet is a combination of 2 active ingredients, oxycodone + acetaminophen, while tramadol is individual.

Their mechanism of action has some differences. Both drugs relieve pain by binding to opioid receptors in the brain. Tramadol also works by inhibiting norepinephrine and serotonin reuptake, while Percocet does not have those actions. However, oxycodone may inhibit transmission of neurotransmitters such as:  dopamine, GABA, substance P, acetylcholine, and norepinephrine.

Tramadol and its metabolites are primarily excreted in the urine with elimination half-lives of 6.3 – 7.4 hours. Oxycodone is also primarily excreted in the urine and its half-life is about 4.5 hours, which means that oxycodone stays in the body for a shorter period of time than tramadol.

Tramadol is rapidly and almost completely absorbed after oral use. Absolute tramadol bioavailability is approximately 75% after oral administration of 100 mg. Maximum plasma concentration of tramadol occurs after two and three hours of administration in healthy adults. Oxycodone is also well absorbed after oral administration with oral bioavailability of 60% to 87%.

Both drugs bind to plasma proteins. Oxycodone’s protein binding is 45% while tramadol’s is 20%.

Tramadol has hepatic metabolism. The primarily metabolic pathways are N- and O- demethylation and glucuronidation or sulfation. One metabolite known as O-desmethyltramadol, or M1 is pharmacologically active in animal models. CYP3A4 and CYP2B6 have their actions in biotransformation of tramadol to N-desmethyl-tramadol.

CYP2D6 facilitates biotransformation of tramadol to active O-desmethyl-tramadol. Oxycodone metabolism is also hepatic.  CYP2D6 facilitates biotransformation of oxycodone to oxymorphone and CYP3A4 facilitates biotransformation of oxycodone to noroxycodone.

Both medicines are used with high efficacy in treatment of moderate to severe acute or chronic pain caused by injury, cancer, osteoarthritis, dental, post-surgical pain and others.  One comparative study has found that the potency ratio of tramadol to oxycodone was approximately 8:1. There was no significant difference in the VAS scores for pain.

It has been also found that tramadol provide adequate analgesia after maxillofacial surgery without risk of respiratory depression. Studies also revealed that the incidence of nausea is slightly greater with tramadol compared to oxycodone. Oxycodone causes significant respiratory depression. On the other hand, tramadol is not associated with respiratory depression.

Tramadol is known to increase levels of serotonin in the body.  If it is overdosed or taken together with other drugs such as antidepressants it can lead to a potentially life-threatening condition known as serotonin syndrome. If it is untreated, serotonin syndrome is a very serious condition that can lead to death.  This syndrome causes muscle spasms and dangerous changes in heart rate, blood pressure, and body temperature.

Compared to Percocet, tramadol may also cause seizure attacks, which is not typical for opioid drugs. The incidence of seizure attack is higher in patients with a history of seizures and those who combine tramadol with antipsychotics, antidepressants, alcohol, or illicit drugs.

Oxycodone is on the other hand, more abusive drug compared to tramadol.  Oxycodone produces a “high” similar to that of heroin.  In one study with heroin-dependent participants oxycodone was described as the “Rolls Royce” of opioids because of producing a “smooth” high.  Long-time users who suddenly stop taking oxycodone suffer from classic symptoms of opiate withdrawal.

Tramadol and Percocet side effects

Tramadol possible side effectsPercocet possible side effects
Constipation (24-46%)Lightheadedness
Nausea (24-40%)Dizziness
Dizziness (10-33%)Drowsiness or sedation
Vertigo (26-33%)Nausea and vomiting
Headache (18-32%)Euphoria
Somnolence (7-25%)Dysphoria
Vomiting (9-17%)Constipation
Agitation (7-14%)Pruritus
Anxiety (7-14%)Skin and urticarial eruptions
Emotional lability (7-14%)Fatal hepatic necrosis (rare; associated with acetaminophen use)
Euphoria (7-14%)Renal tubular necrosis
Hallucinations (7-14%)
Nervousness (7-14%)
Spasticity (7-14%)
Dyspepsia (5-13%)
Asthenia (6-12%)
Pruritus (8-11%)
Diarrhea (5-10%)
Dry mouth (5-10%)
Sweating (6-9%)
Hypertonia (1-5%)
Malaise (1-5%)
Menopausal symptoms (1-5%)
Rash (1-5%)
Urinary frequency (1-5%)
Urinary retention (1-5%)
Vasodilation (1-5%)
Visual disturbance (1-5%)

Which one is expensive, Tramadol or Percocet?

According to

  • The cost for Tramadol 50 mg tablet is around $8 for a supply of 6 tablets
  • The cost for Percocet 2.5/325 mg tablet is around $170 for a supply of 20 tablets
  • The cost for Percocet 5/325 mg tablet is around $230 for a supply of 20 tablets
  • The cost for Percocet 7.5/325 mg tablet is around $250 for a supply of 20 tablets
  • The cost for Percocet 10/325 mg tablet is around $328 for a supply of 20 tablets

Prices depend on the pharmacy you visit. Prices are for cash paying customers only and are not valid with insurance plans.

Warnings and precautions during Tramadol and Percocet use

  • Patient who have severe breathing problems or asthma, stomach or intestines blockage, or patients who have recently use sedatives, tranquilizers, or narcotic medications should not use tramadol and Percocet.
  • In some patients who are on tramadol therapy, seizures may occur. Patients who have epilepsy or other seizure disorder, or a history of head injury, some metabolic disorder or history of alcohol or drug abuse should talk with their doctors about seizure risk before taking tramadol. They should also tell their doctor if they are using certain drugs to treat migraine headaches, muscle spasms, mental illness, depression, nausea and vomiting. These drugs can increase the risk of seizures if they are used together with tramadol at the same time.
  • Tramadol and Percocet will more likely provoke breathing problems in older patients (+65) with severely illness, who are malnourished, or if they have other risk factors.
  • These medicines should never be shared with another person, especially with someone who has a history of drug abuse or addiction.
  • Pregnant patients should never use Tramadol or Percocet; because their babies could gain drug dependency after birth, increasing the risk of life-threatening withdrawal symptoms. Those babies may need medical treatment for several weeks. Patients should tell doctor if they are pregnant or plan to become pregnant.
  • Tramadol can be excreted into breast milk and harm a nursing baby. Patients should not breast-feed after administration of this medicine.
  • Percocet should not be used together with Monoamine oxidase (MAO) inhibitor drugs such as: isocarboxazid, linezolid, selegiline, phenelzine, tranylcypromine, and rasagiline, and also with selective serotonin reuptake inhibitors (SSRIs) such as: fluoxetine, duloxetine, paroxetine because dangerous drug interaction could occur.
  • An overdose of acetaminophen if Percocet is taken in doses of more than 4g per day can damage liver and even cause death. Patients should called doctor if they have pain in their stomach, nauses and loss of appetite, dark urine, clay-colored stools, itching or yellowing of skin and eyes, because those are typical symptoms of acetaminophens hepatotoxicity. In rare cases, acetaminophen may cause a severe skin reaction. Patients should stop taking Percocet and call their doctor if they got rash or redness of the skin that spreads and causes peeling and blistering.

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