Tramadex

/ Dexcel

The dosage should be adjusted according to the severity of pain and the response of the individual patient.
The tablets should be swallowed whole, with a sufficient quantity of liquid and not divided or chewed. The tablets can be taken with or without food. Alternative tablet strengths are available. Where necessary, appropriate tablet strengths should be used to achieve the required dose.It should be taken once every 24 hours as follows:
Adults and adolescents (14 years and over): The starting dose is one 100 mg prolonged-release tablet once daily. The usual dose is one 200 mg prolonged-release tablet once daily, to be taken preferably in the evening. If this does not provide sufficient pain relief, the dosage can be increased in 100 mg dose increments to 300 mg or to a maximum of 400 mg once daily. In general, the lowest effective analgesic dose should be chosen. A daily dose of 400 mg of tramadol should not be exceeded except in special clinical cases. It should not be used for a period longer than absolutely necessary. If continued pain treatment is necessary due to the nature and severity of the illness, careful regular surveillance should be carried out (including periods without treatment, if necessary) in order to determine the need for continued treatment.
Children (under 14): This drugis not recommended for the treatment of children (under 14 years of age).
Elderly patients: Dose adjustment in elderly patients (up to 75 years of age) without clinically relevant hepatic or renal impairment is normally not necessary. In patients over 75 years, the elimination half-life of tramadol may be prolonged. Use in these patients is not recommended.
Renal impairment, dialysis and hepatic impairment: In patients with renal and/or hepatic insufficiency the elimination of tramadol is delayed. In these patients prolongation of the dosage intervals should be carefully considered according to the patient’s requirements. It is not recommended for patients with severe hepatic impairment or with severe renal impairment (creatinine clearance <10 ml/min). Caution is advised in patients with moderate hepatic or moderate renal impairment (creatinine clearance <30 ml/min).
For full details see prescribing information.

Tablets and drops: Moderate to severe pain (short to medium term).

Pregnancy and lactation, hypersensitivity, concurrent administration with MOAI’s or within 14 days of taking. Uncontrolled epilepsy, during rehabilitation from narcotic substances, during acute intoxication from sedatives, sleeping pills, analgesics or other psychotropic drugs. After consuming a quantity of alcohol that causes even slight drunkenness. Severe kidney disease. Children under 14 years.
For full details see prescribing information.

Consumption of alcohol is not recommended during treatment with tramadol. Concomitant treatment with carbamazepine is not recommended. With long-term use, tolerance and psychological and/or physical dependence may develop, even at therapeutic doses. Because of the potential for dependence or withdrawal to occur, the clinical need for continued analgesia should be reviewed regularly. In patients with a tendency to drug abuse or dependence, tramadol should only be used for short periods under strict medical surveillance. Tramadol is 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. Like other opioid agonists, legal or illicit, tramadol can be abused. This should be considered when prescribing or dispensing this drugin situations where the healthcare professional is concerned about a risk of misuse, abuse, or diversion. This drug could be abused by breaking, crushing, chewing, or dissolving the product which can result in the uncontrolled delivery of the opioid, and as a consequence poses a significant risk of overdose and death. Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. Tramadol is not suitable as a substitute in opioid dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms. At therapeutic doses, withdrawal symptoms have been reported with a frequency of 1 in 8,000 while reports of dependence and abuse have been less frequent. Withdrawal symptoms may occur if itis discontinued abruptly. Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous opioid therapy. Clinical experience suggests that signs and symptoms of withdrawal may be avoided by tapering medication when discontinuing tramadol therapy.
Suicide Risk Do not prescribe this drugfor patients who are suicidal or addiction-prone. Prescribe this drugwith caution for patients who are taking tranquilizers or antidepressant drugs and patients who use alcohol in excess and who suffer from emotional disturbance. Serious potential consequences of overdose with this drugare 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.
Respiratory depression or patient taking CNS depressants: Caution is recommended with administration of tramadol in patients at risk for respiratory depression or receiving medicinal products likely to produce respiratory depression. In these patients, alternative non-opioid analgesics should be considered. When 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. Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids or drugs, whether legal or illicit, which cause central nervous system depression. Seizures have been reported in patients receiving tramadol hydrochloride within the recommended dosage range. Spontaneous postmarketing reports indicate that seizure risk is increased with doses above the recommended range. Concomitant use of tramadol hydrochloride increases the seizure risk in patients taking:
Selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), Serotonin-norepinephrine reuptake inhibitors (SNRIs), Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or
Other opioids. Monoamine Oxidase (MAO) inhibitors, Neuroleptics, or Other drugs that reduce the seizure threshold (such as bupropion, mirtazapine, tetrahydrocannabinol).
Risk of convulsions may also be increased in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, certain metabolic disorders, alcohol and drug withdrawal and CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizures. The development of a potentially life-threatening serotonin syndrome may occur with the use of tramadol products, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs, mirtazapine 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.
Serotonin syndrome is likely when one of the following is observed: Spontaneous clonus, Inducible or ocular clonus with agitation or diaphroesis, Tremor and hyperreflexia, Hypertonia and body temperature > 38ºC and inducible or ocular clonus.
Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Treatment depends on the type and severity of the symptoms.
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). Tramadol products in excessive doses, either alone or in combination with other Central Nervous System (CNS) depressants, including alcohol, are a major cause of drug-related deaths. Fatalities within the first hour of overdose are not uncommon. Tramadol should not be taken in doses higher than those recommended by the physician. The judicious prescribing of tramadol is essential to the safe use of this drug. With patients who are depressed or suicidal, consideration should be given to the use of non-narcotic analgesics. Patients should be cautioned about the concomitant use of tramadol products and alcohol because of potentially serious CNS-additive effects of these agents. Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Patients should be advised of the additive depressant effects of these combinations. Many of the tramadol-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts as well as histories of misuse of tranquilizers, alcohol, and other CNS-active drugs. Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of tramadol alone or in combination with other drugs. Patients taking tramadol should be warned not to exceed the dose recommended by their physician. 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 other opioids may be at increased risk and therefore should not receive this drug.
For full details see prescribing information.

The most commonly reported undesirable effects, nausea and dizziness, have been observed in more than 10% of patients. headaches, confusion, tremor, Somnolence, vertigo, anxiety, insomnia, vomiting, dry mouth, diarrhea, dyspepsia, abdominal pain, sweating, pruritus, arthralgia, Fatigue, weakness, anorexia, weight decreased, hot flushes.
For full details see prescribing information.

Tramadex should not be combined with MAO inhibitors.
In patients treated with MAO inhibitors in the 14 days prior to the use of the opioid pethidine, life-threatening interactions on the central nervous system, respiratory and cardiovascular function have been observed. The same interactions with MAO inhibitors cannot be ruled out during treatment with Tramadex. Concomitant administration of Tramadex with other centrally depressant medicinal products including alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics may potentiate the CNS effects.
Tramadex increases the risk of CNS and respiratory depression in these patients. 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. The results of pharmacokinetic studies have so far shown that on the concomitant or previous administration of cimetidine (enzyme inhibitor) clinically relevant interactions are unlikely to occur. Simultaneous or previous administration of carbamazepine (enzyme inducer) may reduce the analgesic effect and shorten the duration of action. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of Tramadex and carbamazepine is not recommended. The combination with mixed agonist/antagonists (e.g. buprenorphine, nalbuphine, pentazocine) and tramadol is not advisable, because the analgesic effect of a pure agonist like tramadol may be theoretically reduced in such circumstances. Tramadol can induce convulsions and increase the potential for selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic anti-depressants, anti-psychotics and other seizure threshold lowering medicinal products (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions. Concomitant therapeutic use of tramadol and serotoninergic drugs, such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors, tricyclic antidepressants, α2-adrenergic blockers, mirtazapine, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, or St. John’s Wort, drugs which impair metabolism of serotonin (including MAOIs), and drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors) may cause serotonin toxicity. This may occur within the recommended dose. If concomitant treatment of Tramadex with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome may include mental-status changes (e.g., confusion, agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia, sweating), neuromuscular aberrations (e.g., hyperreflexia, incoordination, myoclonus) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Serotonin syndrome is likely when one of the following is observed: Spontaneous clonus, Inducible or ocular clonus with agitation or diaphoresis, Tremor and hyperreflexia, Hypertonia and body temperature > 38oC and inducible or ocular clonus.
Withdrawal of the serotoninergic drugs usually brings about a rapid improvement. Treatment depends on the type and severity of the symptoms. Post-marketing surveillance has revealed rare reports of digoxin toxicity and alteration of warfarin effect, including elevation of prothrombin times. Caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (e.g. warfarin) due to reports of increased INR with major bleeding and ecchymoses in some patients. Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors, such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome. Administration of CYP3A4 inducers, such as rifampin and St. John’s Wort, with Tramadex may affect the metabolism of tramadol leading to altered tramadol exposure. In a limited number of studies the pre- or postoperative application of the antiemetic 5-HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain. In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when tramadol is administered concomitantly at therapeutic doses. Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.
For full details see prescribing information.

Pregnancy: Tramadol should not be used during pregnancy unless clearly necessary. In humans, there is insufficient data available to appropriately assess the safety of tramadol use in pregnant women.
Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported during post-marketing surveillance of tramadol immediate-release products.
Lactation: This drugis not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Tramadol and its metabolites have been detected in human breast milk in small amounts. An infant could ingest 0.1% of the single dose given to the mother. A single administration of tramadol does not usually require breastfeeding to be interrupted. If repeated administration is needed for several days, i.e. more than 2 to 3 days, breastfeeding should be suspended. If long-term treatment after birth is necessary, breastfeeding is contraindicated.

Symptoms: In tramadol intoxication, in principle, the same symptoms occur as for all other central acting analgesics (opioids). In particular, these include miosis, vomiting, cardiovascular collapse, loss of consciousness leading to coma, convulsions, respiratory depression leading to respiratory failure, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, bradycardia, hypotension, central nervous system depression, and death. Unexpected effect of overdose: serotonin syndrome has been reported in a context of overdose or abuse with tramadol. Death due to overdose have been reported with abuse and misuse of tramadol, by ingesting, inhaling, or injecting the crushed tablets. The risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol and other CNS depressants, including other opioids.
Treatment: In the treatment of tramadol overdose, primary attention should be given to the re-establishment of a patient airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Emptying of the stomach by means of vomiting (patient to be conscious) or by means of pumping the stomach. Gastric lavage can be considered if the ingestion of overdose is very recent. This must not delay the (repeated) administration of activated charcoal to prevent the absorption of tramadol. While naloxone will reverse some (but not all) symptoms caused by overdose with tramadol, the risk of seizures is also increased with naloxone administration. In animals, convulsions following the administration of toxic doses of tramadol could be suppressed with barbiturates or benzodiazepines but were increased with naloxone. Naloxone administration did not change the lethality of an overdose in mice. Tramadol is only minimally removed from plasma using haemodialysis or haemofiltration. Therefore treatment of acute overdose of tramadol using haemodialysis or haemofiltration alone is not a suitable way of detoxification.