Slideshows Images Quizzes

Ultram

Last reviewed on RxList: 3/16/2017
Ultram Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 03/16/2017

Ultram (tramadol) is a pain reliever (analgesic) used to treat moderate to moderately severe pain in adults. Ultram is available as 50 mg oral tablets. Ultram is available in generic form. Side effects of Ultram include:

  • agitation,
  • nervousness,
  • anxiety,
  • seizures (convulsions),
  • skin rash,
  • dizziness,
  • spinning sensation,
  • hallucinations,
  • fever,
  • fast heart rate,
  • overactive reflexes,
  • nausea,
  • vomiting,
  • upset stomach,
  • diarrhea,
  • constipation,
  • loss of coordination,
  • headache,
  • drowsiness, and
  • fainting.

Good pain management practice dictates that the dose of Ultram be individualized according to patient need using the lowest beneficial dose. Ultram may interact with other drugs including monoamine oxidase inhibitors (MAOIs) and other antidepressant medications. There are no adequate and well-controlled studies of Ultram in pregnant women. Ultram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Ultram passes into breast milk and may harm a nursing baby. Breastfeeding while taking Ultram is not recommended.

Our Ultram Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ultram Consumer Information

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using tramadol and call your doctor at once if you have any of these serious side effects:

  • agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting;
  • seizure (convulsions);
  • a red, blistering, peeling skin rash; or
  • shallow breathing, weak pulse.

Less serious side effects may include:

  • dizziness, spinning sensation;
  • constipation, upset stomach;
  • headache;
  • drowsiness; or
  • feeling nervous or anxious.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Ultram (Tramadol Hcl)

Ultram Professional Information

SIDE EFFECTS

Adverse Drug Reaction Overview

The most commonly reported adverse reactions are dizziness, nausea, constipation, headache, somnolence and vomiting as presented in Table 1.1.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Incidence of Adverse Reactions for ULTRAM® in Chronic Trials of Non-Malignant Pain (Non-titration Trials)

ULTRAM® was administered to 550 patients during the double-blind or open-label extension periods in studies of chronic non-malignant pain. Of these patients, 375 were 65 years old or older. Table 1.1 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days). The most frequently reported events were in the central nervous system and gastrointestinal system. The overall incidence rates of adverse experiences in these trials were similar for ULTRAM® and the active control groups, acetaminophen with codeine, and aspirin with codeine; however, the rates of withdrawals due to adverse events appeared to be higher in the ULTRAM® group. In the tramadol treatment groups, 16.8-24.5% of patients withdrew due to an AE, compared to 9.6-11.6% for acetaminophen with codeine and 18.5% for aspirin with codeine.

Table 1.1: Cumulative Incidence of Adverse Reactions for ULTRAM® in Chronic Trials of Non-Malignant Pain

Percentage of Patients with Adverse Reaction
N = 427
  Up to 7 Days Up to 30 Days Up to 90 Days
Dizziness/Vertigo 26% 31% 33%
Nausea 24% 34% 40%
Constipation 24% 38% 46%
Headache 18% 26% 32%
Somnolence 16% 23% 25%
Vomiting 9% 13% 17%
Pruritus 8% 10% 11%
“CNS Stimulation” a 7% 11% 14%
Asthenia 6% 11% 12%
Sweating 6% 7% 9%
Dyspepsia 5% 9% 13%
Dry Mouth 5% 9% 10%
Diarrhea 5% 6% 10%
a “CNS Stimulation” is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations

Two titration trials showed that the incidence of withdrawal due to AEs could be significantly reduced by using dose titration.

Incidence of Adverse Reactions for ULTRAM® CAPSS-047 Titration Trial

In the double-blind phase of this pivotal trial, gastrointestinal complaints (primarily nausea and vomiting) and dizziness were the adverse events reported most frequently by tramadol-treated subjects, Table 1.2. Most of the adverse events were assessed as mild or moderate in intensity and resolved.

Table 1.2: ´┐ŻAdverse Events in CAPSS-047 - Double-Blind Phase - Frequently Reported ( ≥ 2%a) Adverse Eventsb and Total Incidence of AEs Summarized by WHOART Body System, Treatment Group and Preferred Term

AEs in CAPSS-047 Double-Blind Phase ≥ 2% of patients Tramadol Group/Titration Schedule
Body System 10-days to 200 mg/day
N =54
16-days to 200 mg/day
N =59
13-days to 150 mg/day
N =54
Preferred Term n % n % n %
Any Adverse Event 41 75.9 41 69.5 33 61.1
Body as a Whole - General Disorders
  Influenza-like symptoms 0 0.0 2 3.4 0 0.0
  Pain 1 1.9 2 3.4 0 0.0
  Fatigue 0 0.0 0 0.0 2 3.7
Central and Peripheral Nervous System Disorders
  Dizziness 4 7.4 4 6.8 4 7.4
  Headache 10 18.5 9 15.3 7 13.0
Gastrointestinal System Disorders
  Mouth Dry 0 0.0 1 1.7 3 5.6
  Constipation 4 7.4 2 3.4 6 11.1
  Diarrhea 4 7.4 3 5.1 1 1.9
  Vomiting 10 18.5 7 11.9 4 7.4
  Nausea 29 53.7 25 42.4 18 33.3
Psychiatric Disorders
  Insomnia 1 1.9 2 3.4 2 3.7
  Somnolence 5 9.3 4 6.8 0 0.0
Reproductive Disorders, Female
  Menstrual Disorder 0 0.0 2 2.0 0 0.0
Reproductive Disorders, Male
  Epididymitis 0 0.0 0 0.0 1 11.1
Respiratory Systems Disorders
  Coughing 0 0.0 3 5.1 0 0.0
  Sinusitis 1 1.9 2 3.4 2 3.7
  Upper Resp Tract Infection 2 3.7 0 0.0 0 0.0
Skin and Appendages Disorders
  Pruritus 2 3.7 1 1.7 4 7.4
  Rash 0 0.0 2 3.4 2 3.7
a Preferred terms reported by ≥ 2% of subjects in one or more treatment groups, intent-to-treat population.
b Number of patients with adverse event; numbers shown are all events regardless of relationship to study drug.

Incidence 1% to less than 5% possibly causally related: the following lists adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a causal relationship with ULTRAM® exists.

Body as a Whole: Malaise

Cardiovascular: Vasodilation.

Central Nervous System: Anxiety, Confusion, Coordination disturbance, Euphoria, Miosis, Nervousness, Sleep disorder.

Gastrointestinal: Abdominal pain, Anorexia, Flatulence.

Musculoskeletal: Hypertonia.

Skin: Rash.

Special Senses: Visual disturbance.

Urogenital: Menopausal symptoms, Urinary frequency, Urinary retention.

Incidence less than 1%, possibly causally related: the following lists adverse reactions that occurred with an incidence of less than 1% in clinical trials and/or reported in post-marketing experience.

Body as a Whole: Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency, Weight loss, Serotonin syndrome (mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma).

Cardiovascular: Orthostatic hypotension, Syncope, Tachycardia.

Central Nervous System: Abnormal gait, Amnesia, Cognitive dysfunction, Depression, Difficulty in concentration, Hallucinations, Paresthesia, Seizure (see WARNINGS AND PRECAUTIONS), Tremor.

Respiratory: Dyspnea.

Skin: Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles.

Special Senses: Dysgeusia.

Urogenital: Dysuria, Menstrual disorder.

Other adverse experiences, causal relationship unknown

A variety of other adverse events were reported infrequently in patients taking ULTRAM® during clinical trials and/or reported in post-marketing experience. A causal relationship between ULTRAM® and these events has not been determined. However, the most significant events are listed below as alerting information to the physician.

Cardiovascular: Abnormal ECG, Hypertension, Hypotension, Myocardial ischemia, Palpitations, Pulmonary edema, Pulmonary embolism.

Central Nervous System: Migraine, Speech disorders.

Gastrointestinal: Gastrointestinal bleeding, Hepatitis, Stomatitis, Liver failure.

Laboratory Abnormalities: Creatinine increase, Elevated liver enzymes, Hemoglobin decrease, Proteinuria.

Sensory: Cataracts, Deafness, Tinnitus.

Other Adverse Experiences Previously Reported in Clinical Trials or Post-Marketing Reports with Tramadol Hydrochloride

Adverse events which have been reported with the use of tramadol products include: allergic reactions (including anaphylaxis, angioneurotic edema and urticaria), bradycardia, convulsions, drug dependence, drug withdrawal (including agitation, anxiety, gastrointestinal symptoms, hyperkinesia, insomnia, nervousness, tremors), hyperactivity, hypoactivity, hypotension, worsening of asthma and respiratory depression. Other adverse events which have been reported with the use of tramadol products and for which a causal association has not been determined include: difficulty concentrating, hepatitis, liver failure, pulmonary edema, Stevens-Johnson syndrome and suicidal tendency.

Serotonin syndrome (whose symptoms may include mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma) has been reported with tramadol when used concomitantly with other serotonergic agents such as SSRIs and MAOIs. Post-marketing experience with the use of tramadol-containing products included rare reports of delirium, miosis, mydriasis, and speech disorder, and very rare reports of movement disorder including dyskinesia and dystonia.

Cases of hypoglycemia have been reported in patients taking tramadol, mostly in patients with pre-disposing risk factors, including diabetes, elderly and renal insufficiency. Caution should be exercised when prescribing tramadol to diabetic patients. More frequent monitoring of blood glucose levels may be appropriate, including at initiation or dose increase.

Drug Abuse, Addiction And Dependence

Tramadol may induce psychic and physical dependence of the morphine-type (μ-opioid) (see WARNINGS AND PRECAUTIONS, Drug Abuse, Addiction and Dependence). Dependence and abuse, including drug-seeking behaviour and taking illicit actions to obtain the drug are not limited to those patients with a prior history of opioid dependence. The risk in patients with substance abuse has been observed to be higher. Tramadol is associated with craving and tolerance development.

A Risk Management program to support the safe and effective use of ULTRAM® has been established. The following are considered to be the essential components of the Risk Management program:

  1. Commitment to not emphasize or highlight the scheduling status of ULTRAM® (i.e., not listed under a schedule to the CDSA) in its advertising or promotional activities.
  2. Inclusion of a PAAB-approved fair balance statement in all ULTRAM® advertising and promotional materials.
  3. Assurance that health-care education activities on pain management with ULTRAM® include balanced, evidence-based and current information. Commitment to take reasonable actions to inform health-care professionals that there is Health Canada-approved patient information on benefits and risks, and to ensure that this information can be readily accessed through electronic and/or hard copy sources.

Withdrawal Symptoms

Withdrawal symptoms may occur if ULTRAM® is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely, hallucinations. Other symptoms that have been seen less frequently with ULTRAM® discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be relieved by reinstitution of opioid therapy followed by a gradual, tapered dose reduction of the medication combined with symptomatic support.

Read the entire FDA prescribing information for Ultram (Tramadol Hcl)

Health Solutions From Our Sponsors