Tramadol HCL (Ultram) Side Effects, Dosage, Abuse | Van Voong, PharmD | RxEconsult

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What is Tramadol Hydrochloride (Ultram) Category: Pain Management by - June 6, 2013 | Views: 39562 | Likes: 1 | Comment: 0  

What is Tramadol HCL?

Tramadol hydrochloride (HCL) is an oral prescription drug used to treat moderate to moderately severe pain in adults. Tramadol, like morphine, relieves pain by binding to pain receptors (opioid receptors) in the brain and spinal cord, reducing the transmission of pain signals. 

Tramadol brands

Ultram is the original brand name version of generic tramadol.  It is manufactured by Janssen Ortho, LLC and was approved in March 1995.  Generic tramadol is available from other manufacturers, including Amneal Pharms, Zydus Pharms Inc, Mylan Pharms Inc, Watson Labs, Mallinckroft, Teva and many more.

ConZip, Rybix ODT, FusePaq Synapryn and Ryzolt are the other brands of generic tramadol.

Tramadol dosage and preparations

Ultram is the immediate release formulation and available in 50 mg tablets.  Immediate release tablet releases the active ingredient in a short time period and are usually prescribed more than once a day.  

Ultram ER is the extended release formulation and available in 100, 200, and 300 mg tablets. Extended release tablet releases the active ingredient over a long time period and are prescribed once a day.  Extended release formulations are typically used for treatment of chronic pain, which requires around-the-clock treatment.

For treatment of moderate to moderately severe pain, Ultram (tramadol) is dosed 50 to 100 mg by mouth every four to six hours as needed following initial titration.  The initial titration dose is 25 mg per day every morning and increasing the dose by 25 mg increments as separate doses every 3 days to reach 100 mg per day (or 25 mg four times a day).   The total daily dose may be increased by 50 mg every 3 days as tolerated to reach 200 mg per day. The maximum daily dose is 400 mg.

Ultram ER (tramadol extended release) is dosed 100 mg by mouth once a day and used for treatment of chronic pain.  The dose may be increased by 100 mg increments every 2 to 3 days if needed.  The maximum daily dose is 300 mg.

Tramadol can be taken with or without food.

How effective is Tramadol

In patients following oral surgery, pain relief was seen at doses of 50 mg and 75 mg.  A dose of tramadol 100 mg provides pain relief greater than that of codeine sulfate 60 mg, but less effective than the combination of aspirin 650 mg with codeine phosphate 60 mg.

Patients with chronic painful condition were studied in three control trials of one to three months duration.  The average daily dose of approximately 250 mg of tramadol taken in divided doses were found to be comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg (Tylenol with Codeine #3) daily, five doses of aspirin 325 mg with codeine phosphate 30 mg daily, or two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (Tylox) daily.

Pain relief begins approximately within 1 hour after taking tramadol. 

Tramadol side effects

Common side effects: dizziness, nausea, vomiting, constipation, headache, sleepiness, and itching

Serious side effects: heart attack, pancreatitis, allergic reactions, seizure, and difficulty breathing


Patients with hypersensitivity to tramadol or opioids should not take tramadol.

Do not take tramadol in situations where opioids are contraindicated and during acute intoxication of alcohol, hypnotics (drugs that cause sleepiness), narcotics, pain relievers, opioids, or psychotropic drugs. Psychotropic drugs affect the brain function and can alter perception, mood, consciousness, cognition, and behavior. Tramadol may worsen respiratory depression and brain function in these patients.


Seizure Risk: Seizures can occur when taking recommended doses of tramadol.  The risk for seizures increases when taking higher than recommended doses of tramadol.  Taking tramadol with selective serotonin reuptake inhibitors (for example, Prozac), monoamine oxidase inhibitors (for example, phenelzine), tricyclic antidepressants (for example, amitriptyline), or other opioids can also increase risk of seizures.

Suicidal risk: Patients who are suicidal or prone to addiction should not use Tramadol. Deaths related to tramadol have occurred in patients who have a history of emotional disturbances, suicidal behaviors, and misuse of alcohol and sedating drugs. 

Report unusual changes in behavior, worsening depression or suicidal thoughts to a physician or pharmacist.

Serotonin syndrome: Serotonin syndrome may occur when taking tramadol.  Serotonin syndrome is the consequence of excess serotonin activity in the body. Serotonin syndrome can cause death. 

The risk for serotonin syndrome increases when using tramadol with drugs that increase serotonin such as triptans (for example, sumatriptan or Imitrex), SSRIs, and MAOIs.  Drugs that impair the metabolism of tramadol can also increase the risk of serotonin syndrome.  Symptoms of serotonin syndrome may include mental changes (for example, agitation, hallucination, confusion, coma), increased heart rate, blood pressure changes, incoordination, nausea, vomiting and diarrhea.

Anaphylactoid reactions (serious allergic reactions): Tramadol is not to be taken by patients with hypersensitivity to tramadol or opioids.  Serious and rarely fatal anaphylactoid reactions have occurred and often following the first dose.  Anaphylactoid reactions are serious allergic reactions that occur rapidly and can cause death.

Serious allergic reactions include itchy rash, hives, difficulty breathing, shortness of breath, low blood pressure or swelling of the lips, tongue or throat.

Respiratory depression: Patients who are at risk for respiratory depression should take tramadol cautiously.  Respiratory depression can occur when taking large doses of tramadol with anesthetic medications or alcohol. 

Mental and physical impairment: Do not perform hazardous tasks or operate heavy machinery or car when taking tramadol.  Mental and physical abilities may be impaired when taking tramadol. 

Intracranial pressure or Head trauma: Use caution in patients with increased intracranial pressure or head injury.  Tramadol can cause respiratory depression and altered mental status.  Respiratory depression may cause retention of carbon dioxide and increase in cerebrospinal fluid pressure.  

Overdose risk: Overdose can occur when taking tramadol with alcohol or drugs that affect the central nervous system or more than the recommended dose.  The potential serious consequences of tramadol overdose are slowed respiratory or heart rate, constricted pupils, seizures, loss of consciousness and death.

 Withdrawal: Withdrawal symptoms can occur if tramadol is abruptly stopped.  Withdrawal symptoms include anxiety, sweating, difficulty sleeping, pain, nausea, tremors, diarrhea, difficult breathing and sometimes hallucinations.  Withdrawal symptoms can be avoided by gradually decreasing the dose.

Drug interactions: Tramadol is metabolized by liver enzymes in the body.  Taking tramadol with drugs that inhibit the metabolism of tramadol results in higher levels of tramadol in the body.  High levels of tramadol increase the risk for serious side effects including seizures or serotonin syndrome.  Some examples of drugs that inhibit tramadol’s metabolism include quinidine, fluoxetine, paroxetine, amitriptyline, ketoconazole and erythromycin.

Carbamazepine will reduce the pain relieving effects of tramadol by increasing metabolism of tramadol.  In addition, carbamazepine is not recommended because tramadol may cause seizures.

Use tramadol with caution when taking with central nervous system depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines (for example prochlorperazine or Compazine), or sedative hypnotics.

Misuse, abuse, and diversion

Tramadol has the potential for misuse and abuse.  Misuse and abuse of tramadol can increase risk of overdose and death. According to the Drug Abuse Warning Network (DAWN), in 2010, 16,251 emergency department visits involved non-medical use of tramadol and from 2004 to 2010 non-medical use of tramadol visits increased by 235%.

DAWN defines non-medical use as the misuse or abuse of any therapeutic substance and includes the following:

  • taking more than the prescribed dose of a prescription drug;
  • taking more than the recommended dose of an over-the-counter pharmaceutical or supplement;
  • taking a drug prescribed for another individual;
  • taking a drug obtained illegally or without a legitimate prescription;
  • deliberate poisoning with a pharmaceutical by another person; and
  • any use of a prescription drug, an over-the-counter pharmaceutical, or a dietary supplement that ED medical staff document in the patient's medical record as misuse or abuse.

Addiction to tramadol may occur and includes behaviors such as lack of control over drug use, compulsive use, use for non-medical purposes and craving.  Tramadol has been found to cause dependence. Gradual reduction of the dose is recommended to prevent withdrawal symptoms. Tramadol is associated with tolerance, which is the need for increasing the dose in order to achieve the pain reducing effects.  

Until August 18, 2014, tramadol was a schedule IV controlled drug only in Arkansas, Illinois, Kentucky, Mississippi, New Mexico, New York, North Dakota, Ohio, Oklahoma, Tennessee, West Virginia and Wyoming. The DEA switched tramadol to a schedule IV controlled drug in all states to combat drug addiction and diversion and this change took effect on August 18, 2014. 


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Duke AN, Bigelow GE, Lanier RK, Strain EC. Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther. 2011;338:255–62.

Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacological comparison of tramadol and morphine. Drug and Alcohol Dependence. 1991;27, 7–17.

Raffa, R. B. Basic Pharmacology Relevant to Drug Abuse Assessment: Tramadol as Example. Journal of Clinical Pharmacy and Therapeutics. 2008;101-08.

Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2010: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 12-4733, DAWN Series D-38. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012

Thomson Reuters Micromedex Clinical Evidence Solutions. Thomson Reuters. RED BOOK Online Drug References. Web. 30 May 2013.

Ultram FDA prescribing information

Unites States, Drug Enforcement Agency. Office of Diversion Control. Tramadol (Trade Names: Ultram, Ultracet). Mar. 2013. Web. 30 May 2013.

Article Updated: 8/18/2014

This medication summary is for information only and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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