Sign Out
In patients sensitive to opiates the product should only be used with caution.
Care should be taken when treating patients with respiratory depression, or if concomitant CNS depressant drugs are being administered, or if the recommended dosage is significantly exceeded as the possibility of respiratory depression cannot be excluded in these situations.
Convulsions have been reported in patients receiving Tramadol at the recommended dose levels. The risk may be increased when doses of Tramadol exceed the recommended upper daily dose limit (400 mg). In addition, Tramadol may increase the seizure risk in patients taking other medicinal products that lower the seizure threshold. Patients with epilepsy or those susceptible to seizures should only be treated with Tramadol if there are compelling circumstances.
Tolerance, psychological and physical dependence may develop, especially after long-term use. In patients with a tendency to drug abuse or dependence, treatment with Tramadol should only be carried out for short periods under strict medical supervision.
ZYROTRAM Injection is not a suitable substitute in opioid-dependent patients. Although it is an opioid agonist, Tramadol cannot suppress morphine withdrawal symptoms.
When a patient no longer requires therapy with Tramadol, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
CYP2D6 metabolism: Tramadol is metabolised by the liver enzyme CYP2D6. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect may not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an ultra-rapid metaboliser there is a risk of developing side effects of opioid toxicity even at commonly prescribed doses.
General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. Estimates of prevalence of ultra-rapid metabolisers in different populations are summarised as follows: (see table.)
Click on icon to see table/diagram/imageRisk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of Zyrotram Injection and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Tramadol hydrochloride 50 mg/ml solution for injection or infusion concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms.
Respiratory depression: Administer ZYROTRAM cautiously in patients at risk for respiratory depression, including patients with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, in these patients, even therapeutic doses of ZYROTRAM 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.
Effects in Ability to Drive and Use Machines: Even when taken according to instructions, Tramadol hydrochloride 50 mg/ml solution for injection or infusion may cause effects such as somnolence and dizziness and therefore can impair cognitive function and can affect a patient's ability to drive safely. This applies particularly in conjunction with alcohol and other psychotropic substances. Patients should, therefore, not drive or operate machinery.
Use in Children: The safety and efficacy of ZYROTRAM has not been studied in the paediatric population. Therefore, use of ZYROTRAM is not recommended in patients under 12 years of age.
Post-operative use in children: There have been reports in the published literature that Tramadol given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events. Extreme caution should be exercised when Tramadol is administered to children for post-operative pain relief and should be accompanied by close monitoring for symptoms of opioid toxicity including respiratory depression.
Children with compromised respiratory function: Tramadol is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of opioid toxicity.
