Each Controlled Release Capsule contains: Tramadol Hydrochloride B.P 100 mg.
Permitted colours used in capsule shell.
Pharmacology: Tramadol hydrochloride is a centrally acting analgesic with binding to specific opioid receptors. It is a non-selective, pure agonist at mu (μ), delta (δ) and kappa (K) opioid receptors with a higher affinity for the u receptor. Other mechanisms, which may contribute to its analgesic effect, are inhibition of neuronal re-uptake of noradrenaline and serotonin. Tramadol hydrochloride does promote the release of histamine. Tramadol hydrochloride is well absorbed after oral or rectal administration, with an absorption half-life (T1/2ka) of an immediate release formulation of 0.38 ± 0.18 hours. The mean systemic bioavailability is 68%. Tramadol hydrochloride crosses the blood-brain and placenta barrier. Only very small amounts are excreted in breast milk unchanged or as metabolite. The elimination half-life of an immediate formulation is 5 to 7 hours. Tramadol hydrochloride is mainly metabolized in the liver (90%).
Tramadol hydrochloride and its metabolites are almost excreted by the renal route (95%). Billiary excretion of these components is quantitatively insignificant and is therefore subject to hepatic metabolism and renal elimination. The terminal half-life (T1/2) is likely to be prolonged in impaired hepatic or renal function. The increase in the (T1/2) values is relatively low if at least one of these organs is functioning normally.
There are sex differences in the pharmacokinetic parameters of tramadol. The absolute bioavailability was 73% in males and 79% in females. Plasma clearance was 6.4 mL/min/kg in males and 5.73 mL/min/kg in females following a 100 mg i.v. dose. Following a single oral dose and after adjusting for bodyweight, females had a 12% higher peak concentration and 35% higher area under the concentration time curve compared males. The clinical significance of these differences is unknown.
Tramadol hydrochloride (Takol-CR) is used for management of moderate to severe chronic pain.
The dosage should be adjusted to the intensity of pain and the individual's response to the analgesic of Tramadol hydrochloride (Takol-CR).
Adults: Usual dose 1 capsule once or twice daily. The total oral daily dosage should not exceed 400 mg or as prescribed by the physician
Respiratory depression can be antagonized with a pure opiate antagonist (naloxone). If naloxone is to administered, use cautiously because it may precipitate seizures. Treatment of restlessness and/ or convulsions is symptomatic and supportive (benzodiazepines/barbiturates). Tramadol is minimally eliminated from the serum by hemodialysis or hemofiltration. Treatment of acute intoxication with Tramadol hydrochloride (Takol-CR) with hemodialysis or hemofiltration alone is therefore not suitable for detoxification.
Tramadol hydrochloride (Takol-CR) is contraindicated in known hypersensitivity to tramadol hydrochloride or opioids, in acute intoxication with alcohol, hypnotics, analgesics or psychotropic medicines. It should not be administered to patients who are receiving monoamine oxidase inhibitors or within two week of their withdrawal. Tramadol hydrochloride (Takol-CR) must not be used for narcotic withdrawal treatment. Safety during pregnancy and lactation has not been established.
Tramadol hydrochloride (Takol-CR) should not be given to patients with respiratory depression especially in the presence of cyanosis and excessive bronchial secretions. Tramadol hydrochloride (Takol-CR) should be given to patients with increased intracranial pressure or central nervous system depression due to head injury or cerebral disease.
The administration of Tramadol hydrochloride (Takol-CR) concurrently with central nervous system depressant medicines is likely to intensify and prolong CNS effects. Patients should be warned not to operate machinery or drive a car while using Tramadol hydrochloride (Takol-CR).
Seizures: Seizures have been reported in patients receiving Tramadol at dosages within the recommended dosage range. The risk of seizures is enhanced ion patients exceeding the recommended dose, or in patients taking tricyclic anti-depressants or other tricyclic compounds e.g. promethazine, selective serotonin re-uptake inhibitors, MAO-inhibitors and neuroleptics. The risk of seizures may also be increased in patients with epilepsy, with a history of seizures or in patients with recognized risk of seizures e.g. drug and alcohol withdrawal and intracranial infections, head trauma, metabolic disorders and naloxone administration with Tramadol overdose. Patients known to suffer from cerebral convulsions should be carefully monitored during treatment with Tramadol hydrochloride (Takol-CR).
Drug Abuse and Dependence: Although Tramadol has a low dependence potential, tolerance, psychic and physical dependence of the morphine-type (u opioid) may develop with long term use. The drug has been associated with craving, drug-seeking behavior and tolerance development. Cases of abuse and dependence on Tramadol have been reported. Tramadol hydrochloride (TakolCR) should not be use in opioid- dependent patients. Tramadol hydrochloride (Takol-CR) can reinitiate physical dependence in patients who have been previously dependent on or chronically using other opioids. In patients with a tendency to drug abuse, a history of drug dependence or who are chronically using opioids, treatment with Tramadol hydrochloride (Takol-CR) is recommended.
Effects on ability to drive or operate machinery: Tramadol hydrochloride (Takol-CR), may affect reactions to the extent that driving ability and the ability to operate machinery may be impaired. This applies particularly in conjunction with other psychotropic medicines including alcohol.
Tramadol hydrochloride (Takol-CR) should be used with caution in patients with severe impairment of hepatic and renal function and in patients prone to convulsive disorders or in shock.
Dependence and Withdrawal: Repeated use of opioids is associated with the development of psychological and physical dependence. Although this is less of a problem with legitimate therapeutic use, dependence may develop rapidly when opioids are regularly abused for their euphoriant effects. Drug dependence of the opioid type is characterized by an overwhelming need to keep taking the drug (or one similar properties), by physical requirement for the drug in order to avoid withdrawal symptoms, and by a tendency to increase the dose owing to the development of tolerance.
Abrupt withdrawal of opioids from person physically dependent on them precipitates a withdrawal syndrome, the severity of which depends on the individual, the drug used, the size and frequency of the dose, and duration of drug use. Withdrawal symptoms may also follow the use of an opioid antagonist such as naloxone or mixed agonist and antagonist such as pentazocine to opioid dependence person. Neonatal abstinence syndrome may occur in the offspring of opioid dependent mothers and these infants can suffer withdrawal symptoms at birth.
Opioid analgesic can be classified according to the receptors at which they act and withdrawal syndromes are characteristics for a receptor type. Cross-tolerance and cross-dependence can be expected between opioids acting at the same receptors, Dependence associated with morphine and closely related μ-agonist appears to result in more severe withdrawal symptoms than that associated with k-receptor agonist, Onset and duration of withdrawal symptoms also vary according to the duration of the specific drug. With morphine and diamorphine withdrawal symptoms usually begin within a few hours, reach a peak within 36 to 72 hours, and then gradually subside; they develop more slowly with methadone. Withdrawal symptoms include yawning, mydriasis, lacrimation, rhinorrhea, sneezing, muscle tremor, weakness, sweating, anxiety, irritability, disturbed sleep or insomnia, restlessness, anorexia, nausea, vomiting, loss of weight, diarrhea, dehydration, leucocytosis, bone pain, abdominal and muscle cramps, gooseflesh, vasomotor disturbances, and increase in heart rate, respiratory rate, blood pressure, and temperature. Some physiological values may not return for several months following the acute withdrawal syndrome.
Withdrawal symptoms may be terminated by a suitable dose of the original or related opioid. Tolerance diminishes rapidly after withdrawal so that the previously tolerated dose may prove fatal.
Interactions with other medicines: Tramadol hydrochloride (Takol-CR) must not be combined with MAO-inhibitor, or within 14 days of discontinuation of it, as potentiation of seratogenic and noradrenergic effects may result. Simultaneous administration with cimetidine is associated with clinically insignificant changes in serum concentrations of tramadol. Therefore, no alteration of the Tramadol hydrochloride (Takol-CR) dosage regimen is recommended for patients receiving chronic cimetidine therapy. Animal studies have shown that the duration of anesthesia is prolonged when tramadol is combined with barbiturates. The analgesic effect and duration of action may be reduced on concomitant or previous use of carbamazepine. The concomitant administration of Tramadol hydrochloride (Takol CR) with centrally acting depressants may produce intensified effects. On the other hand combining Tramadol hydrochloride (Takol-CR) with tranquilizer may produce favorable effects on pain sensation and management.
Information for Patient: Tramadol hydrochloride (Takol-CR) is a potent drug for the relief of pain, e.g. in wound pain, fractures, severe pain, tumor pain, heart attack. It should not be used for minor pain. The effect sets quickly and lasts for some hours.
The following side-effects have been reported: Gastrointestinal system:
Nausea, vomiting, dry mouth, heartburn, constipation, abdominal discomfort, diarrhea.
Central Nervous System and Psychiatric:
Fatigue, sedation, drowsiness, dizziness, confusion, hallucinations, seizures.
Sweating, skin rashes, bradycardia, tachycardia, flushing, bronchospasm, angioedema, syncope, paraesthesia, anaphylaxis and anaphylactic reactions have been reported. These reactions may occur after the first dose. Postural hypotension or cardiovascular collapsed has been observed, potential for Toxic Epidermal Necrolysis and StevensJohnson syndrome. Tramadol hydrochloride (Takol-CR) should not be used for the treatment of minor pain.
Tramadol can increase the potential for selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), anti-psychotics and other seizure threshold lowering drugs to cause convulsions. If concomitant treatment of tramadol 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. Concurrent administration of tramadol with other centrally acting drugs, including alcohol, centrally acting analgesics, opioids and psychotropic drugs may potentiate CNS depressant effects. Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of tramadol and carbamazepine is not recommended. Tramadol is metabolized to M1 by the CYP2D6 P450 isoenzyme. Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and tramadol results in increased concentrations of tramadol and reduced concentrations of M1. Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors such as quinidine, fluoxetine, paroxetine, 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. Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity and rare alterations of warfarin effect, including elevation of prothrombin times based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when tramadol is coadministered with a triptan.
Store at temperatures not exceeding 30°C.
N02AX02 - tramadol ; Belongs to the class of other opioids. Used to relieve pain.
CR cap 100 mg x 30's, 100's.