warnings and cautions
5 WARNINGS AND PRECAUTIONS Seizures: Can occur within the recommended dose range. Concomitant use with certain other drugs may increase the seizure risk. Risk of convulsions may increase in patients with epilepsy, history of seizures, and with a recognized risk for seizure. ( , ) 5.1 5.9 Suicide: Do not prescribe for suicidal or addiction-prone patients. ( ) 5.2 Serotonin Syndrome: May be life-threatening. Can occur with tramadol alone or with concomitant use of other serotonergic drugs or those that inhibit metabolism of tramadol. ( . ) 5.3 5.9 Anaphylactoid Reactions: Serious and rarely fatal anaphylactoid reactions have occurred. Increased risk in patients with history of anaphylactoid reactions to other opioids. ( ) 5.4 Hypersensitivity reactions: Serious and rarely fatal anaphylactoid reactions have occurred, often after the first dose. Other reactions include pruritus, hives, bronchospasm, angioedema, TEN, SJS. ( ) 5.4 Respiratory Depression: Administer cautiously in patients at risk for respiratory depression. ( ) 5.5 CNS Depression: Use with caution and in reduced dosages in patients taking CNS depressants and in patients at risk for CNS depression. Patients should not consume alcohol-containing beverages while using Tramadol Hydrochloride Extended-Release ( , ) 5.6 5.12 Increased Intracranial Pressure or Head Trauma: Use with caution in patients with increased intracranial pressure or head injury. ( ) 5.7 Ambulatory Patients: Tramadol may impair mental and/or physical abilities required for potentially hazardous tasks. ( ) 5.8 Tapering may reduce withdrawal symptoms. ( ) 5.10 Misuse, Abuse, and Diversion: Tramadol can be abused in a manner similar to other opioid agonists, legal or illicit. ( ) 5.11 Overdosage can cause CNS and respiratory depression and death. ( ) 5.13 Tramadol Hydrochloride Extended-Release may complicate clinical assessment of acute abdominal conditions. (5.14) 5.1 Seizure Risk Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking: [see DRUG INTERACTIONS ( , )] 7.1 7.2 Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants or anorectics, Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), Other opioids, MAO inhibitors [see WARNINGS AND PRECAUTIONS ( ) and DRUG INTERACTIONS ( )], 5.9 7.1 Neuroleptics, or Other drugs that reduce the seizure threshold. Risk of seizures may also increase 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). In tramadol overdose, naloxone administration may increase the risk of seizure. 5.2 Suicide Risk Do not prescribe Tramadol Hydrochloride Extended-Release for patients who are suicidal or addiction-prone. Consideration should be given to the use of non-narcotic analgesics in patients who are suicidal or depressed [see DRUG ABUSE AND DEPENDENCE ( ) 9.2 ]. Prescribe Tramadol Hydrochloride Extended-Release with caution for patients with a history of misuse and/or are taking CNS-active drugs including tranquilizers or antidepressant drugs, or alcohol in excess, and patients who suffer from emotional disturbance or depression [see DRUG INTERACTIONS ( )]. 7.4 Tell your patients not to exceed the recommended dose and to limit their intake of alcohol . [see DOSAGE AND ADMINISTRATION ( ) and WARNINGS AND PRECAUTIONS ( )] 2.1 5.6 5.3 Serotonin Syndrome Risk The development of a potentially life-threatening serotonin syndrome may occur with use of tramadol products, including Tramadol Hydrochloride Extended-Release , 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). This may occur within the recommended dose. . [see CLINICAL PHARMACOLOGY ( )] 12.3 Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). 5.4 Anaphylactoid Reactions Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with tramadol. When these events do occur it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis and Stevens-Johnson syndrome. Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive Tramadol Hydrochloride Extended-Release [see CONTRAINDICATIONS ( )]. 4 5.5 Respiratory Depression Administer Tramadol Hydrochloride Extended-Release cautiously in patients at risk for respiratory depression. In these patients alternative non-opioid analgesics should be considered. If large doses of tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Respiratory depression should be treated as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures . [see WARNINGS AND PRECAUTIONS ( ) and OVERDOSAGE ( )] 5.1 10 5.6 Interaction With Central Nervous System (CNS) Depressants, Including 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. Use Tramadol Hydrochloride Extended-Release 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. Tramadol Hydrochloride Extended-Release increases the risk of CNS and respiratory depression in these patients. Alcohol-containing beverages should not be consumed by patients using Tramadol Hydrochloride Extended-Release . [see WARNINGS AND PRECAUTIONS ( ), DRUG INTERACTIONS ( ), and OVERDOSAGE ( )] 5.6 7.4 10 5.7 Patients with Increased Intracranial Pressure or Head Trauma Use Tramadol Hydrochloride Extended-Release with caution in patients with increased intracranial pressure or head injury. The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in these patients. Additionally, pupillary changes (miosis) from tramadol may obscure the existence, extent, or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating altered mental status in these patients if they are receiving Tramadol Hydrochloride Extended-Release . [see WARNINGS AND PRECAUTIONS ( )] 5.5 5.8 Use in Ambulatory Patients Tramadol Hydrochloride Extended-Release may impair the mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Caution patients initiating therapy with Tramadol Hydrochloride Extended-Release or those whose dose has been increased to refrain from potentially hazardous activities until it is established that their mental and physical abilities are not significantly impaired. 5.9 Use With MAO Inhibitors and SSRIs Use Tramadol Hydrochloride Extended-Release with great caution in patients taking monoamine oxidase inhibitors. Animal studies have shown increased deaths with combined administration. Concomitant use of Tramadol Hydrochloride Extended-Release with MAO inhibitors or SSRI's increases the risk of adverse reactions, including seizure and serotonin syndrome . [see WARNINGS AND PRECAUTIONS ( , )] 5.1 5.3 5.10 Withdrawal Symptoms Withdrawal symptoms may occur if Tramadol Hydrochloride Extended-Release is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Clinical experience with other formulations of tramadol suggests that withdrawal symptoms may be reduced by tapering Tramadol Hydrochloride Extended-Release when discontinuing tramadol therapy. 5.11 Misuse, Abuse and Diversion of Opioids Tramadol Hydrochloride Extended-Release contains tramadol, an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Tramadol can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Tramadol Hydrochloride Extended-Release in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Tramadol Hydrochloride Extended-Release could be abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death . [see WARNINGS AND PRECAUTIONS ( ), DRUG ABUSE AND DEPENDENCE ( ), and OVERDOSAGE ( )] 5.13 9 10 Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. The development of addiction to opioid analgesics in properly managed patients with pain has been reported to be rare. However, data are not available to establish the true incidence of addiction in chronic pain patients. Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. 5.12 Risk of Overdosage Serious potential consequences of overdosage with Tramadol Hydrochloride Extended-Release are central nervous system depression, respiratory depression and death. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment [see OVERDOSAGE ( )]. 10 5.13 Acute Abdominal Conditions The administration of Tramadol Hydrochloride Extended-Release may complicate the clinical assessment of patients with acute abdominal conditions.