What are the adverse reactions to tramadol (tramadol hydrochloride)?

From the Guidelines

Tramadol can cause several adverse reactions, including serotonin syndrome, seizures, and respiratory depression, and should be used with caution, especially in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications, as recommended by the most recent guidelines 1.

Adverse Reactions to Tramadol

Tramadol is a weak opioid receptor agonist with some norepinephrine and serotonin reuptake inhibition, used for mild to moderate pain. The medication can cause common side effects such as:

• Nausea
• Vomiting
• Constipation
• Dizziness
• Headache
• Drowsiness
• Dry mouth More serious reactions include:
• Serotonin syndrome (characterized by agitation, hallucinations, rapid heart rate, fever, muscle stiffness, and coordination problems)
• Seizures
• Respiratory depression
• Allergic reactions

Special Considerations

Tramadol also carries a risk of physical dependence and withdrawal symptoms when stopped abruptly. The medication can interact dangerously with:

• Alcohol
• Other opioids
• Certain antidepressants
• Sedatives potentially increasing central nervous system depression. Patients with liver or kidney impairment may experience more severe side effects as the drug accumulates in their system. Elderly patients are typically more sensitive to tramadol's effects.

Dosage Recommendations

The NCCN panel recommends a maximum daily dose of 400 mg for immediate-release formulations (100 mg 4 times a day), or 300 mg/day for extended-release formulations, for adults with normal hepatic and renal function, as stated in the guidelines 1. Lower doses are recommended for older adults (75 years and older) and those with hepatic and/or renal dysfunction to reduce the risk of seizures.

Monitoring and Precautions

If you experience severe side effects, difficulty breathing, or signs of allergic reaction while taking tramadol, seek immediate medical attention. The risk of adverse effects increases with higher doses and longer duration of use, which is why tramadol should be used at the lowest effective dose for the shortest necessary period, as recommended by the guidelines 1.

From the FDA Drug Label

ADVERSE REACTIONS Tramadol hydrochloride was administered to 550 patients during the double-blind or open-label extension periods in U. S. studies of chronic nonmalignant pain. 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 tramadol hydrochloride and the active control groups, ions for Tramadol Hydrochloride in Chronic Trials of Nonmalignant Pain (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’1 7% 11% 14% Asthenia 6% 11% 12% Sweating 6% 7% 9% Dyspepsia 5% 9% 13% Dry Mouth 5% 9% 10% Diarrhea 5% 9% 10%

Adverse Reactions to Tramadol:

• The most common adverse reactions to tramadol include:
  • Dizziness/Vertigo
  • Nausea
  • Constipation
  • Headache
  • Somnolence
  • Vomiting
  • Pruritus
  • CNS Stimulation
  • Asthenia
  • Sweating
  • Dyspepsia
  • Dry Mouth
  • Diarrhea 2 and 2

From the Research

Adverse Reactions to Tramadol

• Tramadol overdose is associated with a significant risk of seizures and respiratory depression, both of which appear to be related to the ingested dose 3
• The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population, but if left untreated, the morbidity and mortality can be high 4
• Long-term utilization of tramadol is associated with various neurological disorders, including seizures, serotonin syndrome, Alzheimer's disease, and Parkinson's disease 5
• Tramadol can produce seizures through inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors 5
• Tramadol is associated with a range of psychological symptoms, including manic episodes, hypomania, serotonin syndrome, psychosis, and cognitive impairment 6

Risk Factors for Adverse Reactions

• Medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors increase the risk of serotonin toxicity and seizures 4
• Age, pre-existing psychiatric conditions, polydrug use, and prolonged tramadol use are risk factors for psychological side effects 6
• Elderly individuals and those with psychiatric histories are particularly vulnerable to tramadol-induced psychological side effects 6

Clinical Presentations and Management

• 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
• Clinicians should closely monitor patients for adverse effects, and further research is needed to understand the mechanisms involved and to reduce the psychological side effects resulting from tramadol use 6