Belcetra Special Precautions

This drug should be used with caution in the following patient: Concurrent use with morphine or repeated administration.
Patients who receives CNS depressants such as opioid, anesthetic, hypnotic, phenothiazine, tranquilizer and sedatives.
Patients with biliary tract disorders.
Patients with hepatic disease.
Patients with renal disease.
Patients with alcohol.
Patients with hypersensitivity to opioid.
Patients with epilepsy or possibility of seizure.
In a state of shock, in an altered state of consciousness for unknown reasons.
General caution: Patients should be advised not to exceed the recommended dose and not to use any other paracetamol (including over the counter) or tramadol hydrochloride containing products concurrently.
Although tramadol hydrochloride develops low onset of the drug dependence, but duration of therapy should be controlled because the possibility of drug dependency in long term use cannot be completely excluded. Drug-dependent patients or patients with the possibility of drug abuse should be carefully observed and it should be taken during short term. Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms. Concomitant use of opioid agonists-antagonists (nalbuphine, buprenorphine, pentazocine) is not recommended.
If tramadol hydrochloride is discontinued abruptly, withdrawal symptoms such as anxiety, sweating, insomnia, spasticity, pain, nausea, tremor, diarrhea, upper respiratory syndrome, piloerection, excitation, nervousness, hyperkinesias or GI disorder may occur. Panic attacks, severe anxiety, hallucination, paresthesias, tinnitus or very rare abnormal CNS reaction have been reported. Clinical experience suggests that withdrawal symptoms may be relieved by tapering the medication.
In patients who took tramadol, allergic reaction such as urticaria, rash, bronchial convulsion, toxic epidermal necrolysis and Steven Johnson's syndrome, including anaphylactoid reaction have been reported. In patients with a history of anaphylactoid to codeine or other opioids, the risk may increase.
Caution should be exercised when this drug is used to patients who take CNS depressant such as alcohol, opioid, anesthetic, hypnotic, phenothiazine, tranquilizer and sedative antidepressant, sedative antihistamines, neuroleptic, centrally acting antihypertensive drug, thalidomide or baclofen, and dosage reduction should be considered. When tramadol is administered to those patients, the risks of CNS and respiratory depression may increase.
Convulsions have been reported in tramadol-treated patients susceptible to seizures or taking other medications that lower the seizure threshold, especially selective serotonin re-uptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia. Epileptic patients controlled by a treatment or patients susceptible to seizures should be treated with this drug only if there are compelling circumstances.
If patients with chronic alcoholism take excessive paracetamol, liver toxicity may occur. This drug is not recommended to patients with liver disease.
In patients with hepatic insufficiency, pharmacokinetic and drug intolerance of this drug have not been studied. Tramadol and paracetamol are mainly metabolized in liver. In patients with severe hepatic disease, this drug is not recommended.
There is no clinical trials of compound of tramadol and paracetamol to renal insufficiency. Bases on tramadol use, degree or rate in excretion of M1, active metabolite of tramadol may be reduced in patients with renal sufficiency. In cases of moderate renal insufficiency (creatinine clearance below 30 ml/min), the dosing should not exceed 2 tablet at 12-hourly intervals.
In long term use, duration of therapy should be controlled or therapy is temporarily discontinued because the possibility of drug dependency cannot be completely excluded.
As medically appropriate, periodic evaluation of prothrombin time should be performed when this drug and warfarin like compounds are administered concurrently due to reports of increased INR.
In one study, use of tramadol during general anaesthesia with enflurane and nitrous oxide was reported to enhance intra-operative recall. Until further information is available, use of tramadol during light planes of anaesthesia should be avoided.
Pediatric and geriatric use: The effective and safe use of this drug have not been established in children below the age of 12 years.
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function; of concomitant disease and multiple drug therapy.
Others: Tramadol showed tolerance in animal study. Therefore, caution is exercised in continuous use or dose increase.
There are no animal or laboratory studies on the combination product (tramadol and paracetamol) to evaluate carcinogenesis, mutagenesis or impairment of fertility.
A slight but statistically significant increase in two common murine tumors, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice. Mice were dosed orally up to 30mg/kg (90mg/m² or 0.5 times the maximum daily human tramadol dosage of 185mg/m²) for approximately two years, although the study was not done with the Maximum Tolerated Dose. This finding is not believed to suggest risk in humans. No such finding occurred in rat carcinogenicity study (dosing orally up to 60mg/kg, 180mg/m², or 1 time the maximum daily human tramadol dosage).
Mutagenic toxicity: Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mutation tests in mice, chromosome aberration test in Chinese hamsters, and bone marrow micronucleus tests in mice and Chinese hamsters. Weekly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans.
Fertility: No effects on fertility were observed for tramadol at oral dose levels up to 50mg/kg (350mg/m²) in male rats and 75mg/kg (450mg/m²) in female rats. These dosages are 1.6 and 2.4 times the maximum daily human tramadol dosage of 185mg/m².
Effects on ability to drive and use machines: Tramadol may cause drowsiness or dizziness, which may be enhanced by alcohol or other CNS depressants. The patient using this drug should be cautioned accordingly.
Use in Pregnancy & Lactation: There are no adequate and well-controlled studies in pregnant women and safety for fetus has not established. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Tramadol and its metabolite are excreted in human milk. Therefore, this drug is not recommended to nursing mothers.