Tramicet Special Precautions

Other risk factors for life-threatening respiratory depression in children: Life-threatening respiratory depression and death have occurred in children who received tramadol. Based upon post-marketing reports with tramadol, children younger than 12 years of age may be more susceptible to the respiratory depressant effects of tramadol. Furthermore, children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to their respiratory depressant effect. Because of the risk of life-threatening respiratory depression and death, avoid the use of Tramicet in adolescents younger than 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
Use with central nervous system (CNS) depressants including alcohol: The concomitant use of tramadol with CNS depressants, including alcohol, may cause additive CNS depressant effects, including profound sedation and respiratory depression. Tramicet should be used with caution and in reduced dosages when administered to patients receiving CNS depressants.
Drug dependence and potential for abuse: Upon repeated administration of opioids, tolerance, physical dependence, and psychological dependence may develop, even at recommended dosages. Tramicet should not be used in opioid-dependent patients. Tramadol has been shown to reinitiate physical dependence in some patients that have been previously dependent on other opioids.
Increased risk of hepatotoxicity with alcohol use: Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use.
Serotonin syndrome with concomitant use of serotonergic drugs: Use Tramicet with great caution in patients taking serotonergic drugs including SSRIs. Concomitant use of tramadol with serotonergic drugs including SSRIs increases the risk of adverse events, including seizure and serotonin syndrome.
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concurrent use of Tramicet with serotonergic drugs (see Interactions). This may occur within the recommended dosage range.
Serotonin syndrome symptoms 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, diarrhoea) and can be fatal (see Interactions). The onset of symptoms generally occurs within several hours to a few days of concomitant use but may occur later than that. Discontinue Tramicet if serotonin syndrome is suspected.
Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, decreased appetite, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement dosing of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
Sexual function/reproduction: Long-term use of opioids may be associated with decreased sex hormone levels and symptoms such as low libido, erectile dysfunction, or infertility.
Respiratory depression: Administer Tramicet cautiously in patients at risk for respiratory depression, including patients with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, as in these patients, even therapeutic doses of Tramicet may decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered. When large doses of tramadol are administered with anaesthetic 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.
Cytochromes P450 (CYP) 2D6 Ultra-Rapid Metabolism: Some individuals may be CYP2D6 ultra-rapid metabolisers. These individuals convert tramadol more rapidly than other people into its more potent opioid metabolites O-desmethyltramadol (M1). This rapid conversion could result in higher than expected opioid-like side effects including life-threatening respiratory depression. The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese, Japanese and Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians, and Arabs. Data are not available for other ethnic groups.
Allergy Alert: Paracetamol may cause severe skin reactions. Symptoms may include skin reddening, blisters or rash. These could be signs of a serious condition. If these reactions occur, stop use and seek medical assistance right away.
Seizure: 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: selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), tricyclic antidepressants (TCAs) and other tricyclic compounds (e.g. cyclobenzaprine, promethazine, etc.) or opioids.
Administration of tramadol may enhance the seizure risk in patients taking: monoamine oxidase inhibitors (MAOIs), neuroleptics or other drugs that reduce the seizure threshold. Risk of convulsion may also increase in patients with epilepsy, those with a history of seizure, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, central nervous system (CNS) infections). In tramadol overdose, naloxone administration may increase the risk of seizure.
Anaphylactoid reactions: Patients with a history of anaphylactoid reactions to codeines and other opioids may be at increased risk and therefore, should not receive Tramicet.
Increased intracranial pressure or head trauma: Tramicet should be used with caution in patients with increased intracranial pressure or head injury.
Treatment withdrawal: Withdrawal symptoms may occur if Tramicet is discontinued abruptly. Panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus, and unusual CNS symptoms have also been very rarely reported with abrupt discontinuation of tramadol hydrochloride. Clinical experience suggests that withdrawal symptoms may be relieved by tapering the medication.
Renal Impairment: In patients with creatinine clearance of less than 30 ml/min, it is recommended that the dosing interval of Tramicet be increased not to exceed 2 tablets every 12 hours. Tramicet is not recommended in patients with creatinine clearance of less than 10 ml/min.
Hepatic Impairment: The use of Tramicet in patients with severe hepatic impairment is not recommended.
Serious Skin Reactions: Rarely, paracetamol may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Hyponatremia: Hyponatremia has been reported very rarely with the use of Tramicet, usually in patients with predisposing risk factors, such as elderly patients and/or patients using concomitant medications that may cause hyponatremia. In some reports, this hyponatremia appeared to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and resolved with discontinuation of Tramicet and appropriate treatment (e.g. fluid restriction). During Tramicet treatment, monitoring for signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.
Risks from Concomitant Use with Benzodiazepines: Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Tramicet with benzodiazepines. Observational studies have demonstrated that concomitant use of opioids and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
If the decision is made to newly prescribe a benzodiazepine and an opioid together, prescribe the lowest effective dosages and minimum durations of concomitant use.
If the decision is made to prescribe a benzodiazepine in a patient already receiving an opioid, prescribe a lower initial dose of the benzodiazepine than indicated in the absence of an opioid, and titrate based on clinical response.
If the decision is made to prescribe an opioid in a patient already taking a benzodiazepine, prescribe a lower initial dose of the opioid, and titrate based on clinical response.
Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when Tramicet is used with benzodiazepines. Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of benzodiazepines.
The recommended dose of Tramicet should not be exceeded.
Tramicet should not be co-administered with other tramadol or paracetamol-containing products.
Effects on Ability to Drive and Use Machine: Tramicet may impair mental or physical abilities require for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Use in Children: The safety and efficacy of Tramicet has not been studied in the paediatric population. Therefore, use of Tramicet is not recommended in patients under 12 years of age.