WARNINGS AND PRECAUTIONS

Seizure Risk
Seizures have been reported in patients receiving tramadol even within the recommended dose range. Seizure risk is increased with tramadol dose above the recommended range. Seizures can also occur after the first dose.

Concomitant use of tramadol increases seizure risk in patients taking:

• SSRI antidepressants or anorectics.
• TCAs, and other tricyclic compounds (e.g., cyclobenzapine, promethazine, etc.)
• MAOIs
• Antipsychotics or neuroleptics (e.g., haloperidol, droperidol, thioridazine)
• Other drugs that reduce seizure threshold
• Other opioids

Administration of tramadol may also increase the risk of convulsions in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). Administration of naloxone for tramadol overdose may increase the risk of seizure.

Anaphylactoid Reactions
Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving tramadol. Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and should not receive tramadol. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, TEN, and SJS. 

Respiratory Depression
Respiratory depression may occur when tramadol is given in large doses with anesthetics and alcohol. Administer tramadol cautiously in patients at risk for respiratory depression. In these patients alternative non-opioid analgesics should be considered.

Interactions with CNS Depressants
Tramadol should be administered with caution and in reduced dosages in patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, or sedative hypnotics. Tramadol increases the risk of CNS and respiratory depression in these patients.

Increased Intracranial Pressure or Head Trauma
Tramadol should be used with caution in patients with increased intracranial pressure or head trauma. The respiratory depressant effects of opiate agonists which include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in these patients. Also, pupillary changes such as miosis from tramadol use may obscure the existence, extent, or course of intracranial pathology.

Acute Abdominal Conditions
The administration of tramadol may complicate the clinical assessment of patients with acute abdominal conditions.

Use in Ambulatory Patients
The use of tramadol may impair mental or physical abilities required for the performance of potentially hazardous tasks (e.g., driving and operating machinery). Patients should not drive a car or any motor vehicle and should not use electrical tools or operate machinery.

Use with MAOIs and SSRIs
Tramadol should be used with great caution in patients taking MAOIs. Concomitant use of tramadol with MAOIs or SSRIs increases the risk of adverse events, including seizure and serotonin syndrome.

Withdrawal
Abrupt discontinuation of tramadol may result in withdrawal symptoms. Anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations have been reported with abrupt discontinuation of tramadol. Withdrawal symptoms may be reduced by tapering the dose.

Patients Physically Dependent on Opioids
Tramadol is not recommended as a substitute in opioid dependent patients. Although it is an opiate-agonist, tramadol cannot suppress opioid withdrawal symptoms.

Exercise caution in the administration of tramadol to patients who have previously received substantial amounts of opioid medications because of the difficulty in assessing dependence in such patients.

Treatment with tramadol should only be carried out for short periods under strict medical supervision in patients with a tendency to drug abuse or dependence.