- Somnolence (excessive sleepiness)
- Pruritus (itchy skin)
- CNS Stimulation
- Asthenia (lack of energy/physical weakness)
- Dyspepsia (increased indigestion)
- Dry Mouth
The following information comes from DailyMed, an FDA label information provider.
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
ADDICTION, ABUSE, AND MISUSE
Tramadol hydrochloride exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing tramadol hydrochloride, and monitor all patients regularly for the development of these behaviors and conditions.
OPIOID ANALGESIC RISK EVALUATION AND MITIGATION STRATEGY (REMS)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
– complete a REMS-compliant education program
– counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
– emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
– consider other tools to improve patient, household, and community safety
LIFE-THREATENING RESPIRATORY DEPRESSION
Serious, life-threatening, or fatal respiratory depression may occur with the use of tramadol hydrochloride. Monitor for respiratory depression, especially during initiation of tramadol hydrochloride or following a dose increase.
Accidental ingestion of tramadol hydrochloride, especially by children, can be fatal.
ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN
Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism. Tramadol hydrochloride is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of tramadol hydrochloride in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
NEONATAL OPIOID WITHDRAWAL SYNDROME
Prolonged use of tramadol hydrochloride during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Concomitant use of opioids with benzodiazepines or other central nervous systems (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
– Reserve concomitant prescribing of tramadol hydrochloride and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
– Limit treatment to the minimum effective dosages and durations.
– Follow patients for signs and symptoms of respiratory depression and sedation
Very common tramadol side effects (> 10% population frequency) include:
Common tramadol side effects (1-10% population frequency) include:
- Mood swings
- Spasticity (muscle tightness, stiffness, or pulling)
- Dry mouth
- Dilation (widening) of blood vessels
- Miosis (excessive pupil constriction)
- Sleep disorder
- Hypertonia (muscle overactivity that leads to rigidity)
- Abdominal pain
- Weight loss
- Vision problems
- Menopausal symptoms
- Frequent urination
- Inability to urinate
Uncommon side effects of tramadol (0.1%-1% population frequency) include:
- Heart regulation abnormalities (e.g., palpitations or cardiovascular collapse)
- Retching (dry heaving)
Rare side effects of tramadol (<0.1% population frequency) include:
- High blood pressure (hypertension)
- Appetite changes
- Pins and needles
- Ringing in the ears
- Allergic reactions/Anaphylaxis
- Heartbeat dropping below 60 BPM
- Hypoventilation (slow and ineffective breathing)
- Involuntary muscle contractions
- Fainting (loss of consciousness)
- Shortness of breath
- Pulmonary embolism (blocked artery in the lungs)
- Blurry vision
- Gastrointestinal bleeding
- Speech problems
- Motor weakness
- Increase in creatinine
- Increase in liver enzymes
- Decrease in hemoglobin
- Pulmonary edema, or “wet lung” (fluid in lungs)
- Hepatitis (liver inflammation)
- Liver failure
- Protein in the urine
- Mouth swelling
- Potentially fatal skin reactions (e.g., toxic epidermal necrolysis)
If you find that any of these side effects of tramadol become severe at any point, or they don’t subside over time, contact your doctor immediately to discuss your alternatives.
The serious adverse reactions of tramadol
- Addiction, Abuse, and Misuse
- Life-Threatening Respiratory Depression (slow and ineffective breathing)
- Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children
- Neonatal Opioid Withdrawal Syndrome
- Interactions with Benzodiazepines or Other CNS Depressants (consult physician/ pharmacist regarding all medications that you take before taking tramadol)
- Serotonin Syndrome
- Adrenal Insufficiency
- Severe Hypotension
- Gastrointestinal Adverse Reactions
- Hypersensitivity Reactions
Clinical Trials Experience
The FDA states that because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of tramadol cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
ULTRAM was administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 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. Although the reactions listed in the table are felt to be probably related to ULTRAM administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication. The overall incidence rates of adverse experiences in these trials were similar for ULTRAM and the active control groups, TYLENOL with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg, however, the rates of withdrawals due to adverse events appeared to be higher in the ULTRAM groups. For more information on the dosage of tramadol, read our dosage page.
Table 1: Cumulative Incidence of Adverse Reactions for ULTRAM in Chronic Trials of Nonmalignant Pain (N=427)
|Up to 7 Days||Up to 30 Days||Up to 90 Days|