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Ultram - Tramal Description : Each Tramal Retard tablet also contains the following excipients: Microcrystalline cellulose, methylhydroxypropylcellulose, colloidal anhydrous silica, magnesium stearate, lactose, polyethylene glycol, propylene glycol, talc and titanium dioxide (E171). Tramadol HCl is (1RS; 2RS) 2-(dimethylaminomethyl)-1-(m-methoxyphenyl)-cyclohexanol hydrochloride. Molecular Formula: C16H25O2N?HCl. MW: 299.8.
Ultram - Tramal Actions : Pharmacology: Tramadol is a centrally acting opioid analgesic. It is a nonselective pure agonist at mc, ? and ? opioid receptors with a higher affinity for the mc receptor. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal re-uptake of noradrenaline and enhancement of serotonin release. Tramadol has an antitussive effect. In contrast to morphine, analgesic doses of tramadol over a wide range have no respiratory depressant effect. Also, gastrointestinal motility is not affected. Effects on the cardiovascular system tend to be slight. The potency of tramadol is reported to be 1/10-1/6 that of morphine. The onset of the analgesic effect of tramadol HCl is rapid and the effect lasts for several hours. Tramadol HCl is a potent drug and should not be used for minor pain. It does not have an anti-inflammatory effect. Tramadol HCl has an analgesic effect in all the usual test models for centrally acting analgesics. On parenteral administration, the intensity of the effect is equivalent to that of other opioid analgesics, eg pentazocine and pethidine. On oral administration, tramadol HCl is practically as effective as on parenteral application. The onset of activity is rapid and the duration of the effect is similar to that of morphine. Tramadol HCl is a pure opiate agonist. The morphine antagonist, naloxone, neutralizes the analgesic effect of tramadol HCl. Pharmacokinetics: Tramal: After oral administration, about 90% of the active substance is absorbed. The absolute bioavailability of oral tramadol is about 68% and about 79% on rectal administration. Peak plasma concentrations are reached about 2 hrs after an oral dose. The high apparent total volume of distribution is proof of the tissue affinity of the active substance. Serum protein-binding is low (about 20%). The elimination half-life in the terminal phase is 6 hrs, with about 1/4-1/3 of the active substance appearing unchanged in the urine. One of the metabolites is pharmacologically active, but the concentration in the blood is lower than that of tramadol HCl itself. Excretion: Tramadol HCl and its metabolites are almost completely eliminated via the kidneys. Tramal Retard: More than 90% of Tramal Retard is absorbed after oral administration. The mean absolute bioavailability is approximately 70%, irrespective of the concomitant intake of food. The difference between absorbed and nonmetabolized available tramadol is probably due to the low first-pass effect. The first-pass effect after oral administration is a maximum of 30%. Tramadol has a high tissue affinity (V?,? = 203 ? 40 L). It has a plasma protein-binding of about 20%. After administration of Tramal Retard 100 mg, the peak plasma concentration Cmax = 141 ? 40 ng/mL is reached after 4.9 hrs. Tramadol passes the blood-brain and placental barriers. Very small amounts of the substance and its O-desmethyl derivative are found in the breast milk (0.1% and 0.02%, respectively of the applied dose). Elimination half-life t?,? is approximately 6 hrs, irrespective of the mode of administration. In patients >75 years, it may be prolonged by a factor or approximately 1.4. In humans, tramadol is mainly metabolized by means of N- and O-demethylation and conjugation of the O-demethylation products with glucuronic acid. Only O-desmethyltramadol is pharmacologically active. There are considerable interindividual quantitative differences between the other metabolites. So far, 11 metabolites have been found in the urine. Animal experiments have shown that O-desmethyltramadol is more potent than the parent substance by the factor 2-4. Its half-life t?,? (6 healthy volunteers) is 7.9 hrs (range 5.4-9.6 hrs) and is approximately that of tramadol. Tramadol and its metabolites are almost completely excreted via the kidneys. Cumulative urinary excretion is 90% of the total radioactivity of the administered dose. In cases of impaired hepatic and renal function, the half-life may be slightly prolonged. In patients with cirrhosis of the liver, elimination half-lives of 13.3 ? 4.9 hrs (tramadol) and 18.5 ? 9.4 hrs (O-desmethyltramadol), in an extreme case 22.3 and 96 hrs, respectively, have been determined. In patients with renal insufficiency (creatinine clearance <5 mL/min) the values were 11 ? 3.2 hrs and 16.9 ? 3 hrs, in an extreme case 19.5 and 43.2 hrs, respectively. Tramadol has a linear pharmacokinetic profile within the therapeutic dosage range. The relationship between serum concentrations and the analgesic effect is dose-dependent, but varies considerably in isolated cases. A serum concentration of 100-300 ng/mL is usually effective.
Ultram - Tramal Indications : Tramal: Moderate to severe acute and chronic pain and in painful diagnostic measures and surgery. Tramal Retard: Moderate to severe pain.
Ultram - Tramal Overdosage : Symptoms: In principle, on intoxication with tramadol, symptoms similar to those of other centrally-acting analgesics (opioids) are to be expected, in particular miosis, vomiting, cardiovascular collapse, reduced level of consciousness up to coma, convulsions and respiratory depression up to respiratory arrest. Treatment: The general emergency measures to keep open the respiratory tract (aspiration), maintenance of respiration and circulation depending on the symptoms apply. The stomach is to be emptied by the induction of vomiting (conscious patient) or rinsed. An antidote for respiratory depression is naloxone. In animal studies, naloxone had no effect on convulsions. In such cases, diazepam should be given.
Ultram - Tramal Contraindication : Known hypersensitivity towards tramadol or any of the excipients of Tramal Retard, in acute intoxications with alcohol, hypnotics, analgesics or psychotropic drugs. Tramal Retard must not be used for narcotic withdrawal treatment. Use in children: Tramal Retard is not suitable for children <14 years.
Ultram - Tramal Warning : Use in Drug-Dependent Patients: Tramal is not suitable as a substitute in opiate-dependent patients. Although Tramal is an opioid agonist, it cannot suppress morphine withdrawal symptoms. Animal experiments have even shown that under certain circumstances, the administration of Tramal may provoke withdrawal syndrome in opiate-dependent monkeys.
Ultram - Tramal Precautions : Tramal/Retard may only be taken with special care in opioid dependence, reduced level of consciousness of uncertain origin, disorders of the respiratory center or function, increased intracranial pressure. The preparation should be used with care in patients with increased reactivity to opioids. Patients known to suffer from cerebral convulsions should be carefully monitored during treatment with Tramal/Retard. Tramadol has a dependence potential. On long-term use, tolerance, psychic and physical dependence may develop. Therefore, in patients with a tendency towards drug abuse or dependence, treatment should only be carried out for short periods under strict medical supervision. Effects on the Ability to Drive or Operate Machinery: Even when used according to instructions, Tramal/Retard may affect reactions to such an extent that road safety and the operation of machinery may be impaired. This applies particularly in conjunction with other psychotropic drugs including alcohol. Use in pregnancy & lactation: There is no experience in pregnant women. Therefore, use of Tramal/Retard during pregnancy is not advised unless the therapeutic benefit outweighs the possible risks. If pain therapy with opioids is indicated during pregnancy, administration is to be limited to single doses of tramadol. Long-term treatment should be avoided during pregnancy as it may lead to habituation and withdrawal symptoms in the neonate. When given before or during birth, tramadol does not affect uterine contractility. In neonates, it may induce changes in the respiratory rate, which are usually not clinically relevant. During lactation, about 0.1% of the tramadol plasma concentration in the mother is excreted in the milk. After a single administration of tramadol, it is not usually necessary to interrupt breastfeeding.
Ultram - Tramal Adverse Reactions : Occasionally, nausea, sweating, dry mouth, dizziness and muzziness may occur. In rare cases, there may be effects on cardiovascular regulation (palpitation, tachycardia, postural hypotension up to cardiovascular collapse). These side effects may occur particularly on IV administration and in patients under physical strain. Moreover, headache, retching, vomiting, constipation, gastrointestinal irritation (eg, feeling of pressure in the stomach, bloating) and dermal reactions (eg, pruritus, exanthema) may occur. In very rare cases, motorial weakness, changes in appetite and micturition disorders have been observed. In very rare cases, various psychic side effects may occur following administration of Tramal Retard which vary individually in intensity and nature (depending on personality and duration of medication). These include changes in mood (usually elation, occasionally dysphoria), changes in activity (usually suppression, occasionally increase) and changes in cognitive and sensorial capacity (eg, decision behavior, perception disorders). In isolated cases, cerebral convulsions have been reported. However, almost all of them occurred after IV administration of high doses of tramadol and concomitant administration of neuroleptics. Allergic reactions and shock cannot definitely be ruled out. Note: Respiratory depression has so far not been observed on the administration of oral tramadol formulations. However, if the recommended dosages are considerably exceeded or other centrally depressant drugs are given concomitantly, the possibility of respiratory depression cannot be entirely excluded.
Ultram - Tramal Drug Interaction : Tramal/Retard must not be combined with MAOIs. On the concomitant administration of Tramal Retard and other centrally depressant drugs, including alcohol, the central effects may be intensified. Animal experiments have shown that the duration of anesthesia is prolonged when tramadol is combined with barbiturates. At the same time, however, combining Tramal/Retard with a tranquilizer, for example, will probably have a favorable effect on pain sensation. On concomitant or previous administration of carbamazepine (an enzyme inducer), the analgesic effect and duration of action may be reduced. Isolated convulsions have been observed on concomitant medication with neuroleptics. Incompatibilities: None.
Ultram - Tramal Storage : Do not store Tramal Retard above 30?C. |
