What are the side effects of Tramadol (tramadol hydrochloride)?

From the Guidelines

Tramadol can cause several serious side effects, including seizures, serotonin syndrome, and allergic reactions, which require immediate medical attention, as noted in the most recent guidelines 1. The side effects of Tramadol (tramadol hydrochloride) are numerous and can be severe. Common side effects include:

• Nausea
• Vomiting
• Constipation
• Dizziness
• Headache
• Drowsiness
• Dry mouth More serious side effects that require immediate medical attention include:
• Seizures
• Serotonin syndrome (characterized by agitation, hallucinations, rapid heart rate, fever, muscle stiffness, and coordination problems)
• Slowed or difficult breathing
• Allergic reactions such as rash, itching, or swelling Tramadol may also cause psychological dependence and physical withdrawal symptoms when stopped abruptly after prolonged use, as reported in studies 1. These withdrawal effects can include:
• Anxiety
• Sweating
• Insomnia
• Rigors
• Pain
• Nausea
• Tremors
• Diarrhea The risk of side effects increases with higher doses and when combined with other medications, particularly other opioids, certain antidepressants, or alcohol, as warned by the guidelines 1. Elderly patients and those with kidney or liver problems may experience more pronounced side effects at standard doses. The maximum daily dose of Tramadol should not exceed 400 mg for adults with normal hepatic and renal function, and lower doses are recommended for older adults and those with hepatic and/or renal dysfunction to reduce the risk of seizures, as recommended by the NCCN panel 1.

From the FDA Drug Label

WARNING Seizures have been reported in patients receiving Tramadol hydrochloride within the recommended dosage range. Serotonin Syndrome Risk The development of a potentially life-threatening serotonin syndrome may occur with the use of tramadol products, including tramadol hydrochloride, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs, and triptans, with drugs which impair metabolism of serotonin (including MAOIs), and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors). Anaphylactoid Reactions Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with tramadol hydrochloride. Respiratory Depression Administer tramadol hydrochoride cautiously in patients at risk for respiratory depression. Interaction With Central Nervous System (CNS) Depressants Tramadol hydrochloride should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. Interactions with Alcohol and Drugs of Abuse Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Increased Intracranial Pressure or Head Trauma Tramadol hydrochloride should be used with caution in patients with increased intracranial pressure or head injury Use in Ambulatory Patients Tramadol hydrochloride may impair the mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Withdrawal Withdrawal symptoms may occur if tramadol hydrochloride is discontinued abruptly

The side effects of Tramadol (tramadol hydrochloride) include:

• Seizures
• Serotonin syndrome
• Anaphylactoid reactions
• Respiratory depression
• CNS depression
• Additive effects with alcohol and other CNS depressants
• Increased intracranial pressure
• Impaired mental and physical abilities
• Withdrawal symptoms 2, 2, 2

From the Research

Side Effects of Tramadol

The side effects of tramadol (tramadol hydrochloride) can be categorized into several areas, including neurological, gastrointestinal, and other effects.

• Neurological side effects:
  • Seizures: Tramadol can produce seizures through inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors 3.
  • Serotonin syndrome: Tramadol's serotonin and norepinephrine reuptake inhibitory effects can result in serotonin syndrome, a potentially life-threatening condition 4.
  • Alzheimer's disease and Parkinson's disease: Long-term utilization of tramadol is associated with various neurological disorders, including Alzheimer's disease and Parkinson's disease 3.
• Gastrointestinal side effects:
  • Nausea and vomiting: The most common adverse events associated with tramadol are nausea and vomiting 5, 6.
  • Constipation: Constipation is also reported as a side effect of tramadol 6.
• Other side effects:
  • Dizziness and drowsiness: Tramadol is associated with a lower incidence of dizziness and drowsiness compared to morphine 5.
  • Respiratory depression: Clinically relevant respiratory depression is rarely observed during tramadol administration at equipotent doses 5.
  • Cardiac depression: Tramadol is associated with a low incidence of cardiac depression 5.
  • Dependence and abuse potential: The dependence and abuse potential of tramadol is negligible 5.

Risk Factors and Management

Certain risk factors, such as medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors, can increase the risk of serotonin syndrome and seizures 4.

• Management of side effects:
  • Serotonin syndrome and seizures can be effectively treated by administering benzodiazepines, providing supportive care, and discontinuing tramadol and other contributing agents 4.
  • Cyproheptadine should be administered in moderate to severe cases of serotonin syndrome 4.
  • Nausea and vomiting can often be prevented by slow injection and administration of a prophylactic antiemetic such as metoclopramid 5.