Tramal® (tramadol hydrochloride) (immediate release) capsules 50 mg, injection 50 mg/mL, 100 mg/2mL
Tramal® Retard tablets (tramadol hydrochloride) (sustained release tablets) 100 mg, 150 mg, 200 mg.
Tramal® 50 mg capsules are green and pale yellow capsules, containing 50 mg tramadol hydrochloride. Excipients include: cellulose-microcrystalline, iron oxide yellow (CI 77492), indigo carmine (CI 173015), titanium dioxide (CI 173015), magnesium stearate, sodium starch glycollate silica-colloidal anhydrous.
Tramal® 50 mg and 100 mg injections contain tramadol hydrochloride 50mg/mL. Excipients include: sodium acetate, Water for Injections.
Tramal® Retard tablets contain: tramadol hydrochloride in the following dose strengths 100, 150 and 200 mg. Excipients are: hypromellose105 mPa.s, silica-colloidal anhydrous, magnesium stearate, microcrystalline cellulose. Excipients in the film coat are: hypromellose 6 mPa.s, lactose, macrogol 6000, propylene glycol, purified talc, titanium dioxide, quinoline yellow aluminium lake CI 47005 (150 and 200 mg tablets only), red iron oxide CI 77491 (150 and 200 mg tablets only), iron oxide yellow
CI 77492 and iron oxide black CI 77499 (200 mg tablet only).
Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioid-like effects. It is not derived from natural sources, nor is it chemically related to opiates. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding to µ-opioid receptors and inhibition of re-uptake of noradrenaline and serotonin. The opioid-like activity of tramadol derives from low affinity binding of the parent compound to µ-opioid receptors and higher affinity binding of the principal active metabolite, O-desmethyltramadol (denoted M1) to µ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. The contribution to human analgesia of tramadol relative to M1 is unknown.
Both animal and human studies have shown that antinociception induced by tramadol is only partially antagonised by the opiate antagonist, naloxone. In addition, tramadol has been shown to inhibit reuptake of noradrenaline and serotonin in vitro, as have some other opioid analgesics. These latter mechanisms may contribute independently to the overall analgesic profile of tramadol.
The analgesic effect is dose-dependant but the relationship between serum concentrations and analgesic effect varies considerably between individuals. In one study, the median serum concentration of tramadol required for effective post-operative analgesia was 300 ng/mL, with individual values ranging from 20 to 990 ng/mL.
Apart from analgesia, tramadol may produce other symptoms similar to that of opioids including; dizziness, somnolence, nausea, constipation, sweating and pruritus. However, tramadol causes significantly less respiratory depression than morphine. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no clinically significant effect on heart rate, left ventricular function or cardiac index. Orthostatic changes in blood pressure have been observed.
Tramadol is administered as a mixture of two stereoisomers; the following information refers to the combined concentration of both isomers. Tramadol has a linear pharmacokinetic profile within the therapeutic dosage range.
Tramadol is rapidly and almost completely absorbed after oral administration of 50 mg capsules following a mean absorption delay (t0) of approximately thirty minutes. The absorption half-life (t½) is 23 ± 10 minutes.
After oral administration of two 50 mg capsules, the mean absolute bioavailability (fabs) is 68-72%, and the peak serum level (Cmax) is reached approximately two hours after administration. The mean peak plasma concentration (Cmax) is approximately 280 ng/mL after oral administration of two 50 mg capsules. Oral administration of tramadol with food does not significantly affect its rate or extent of absorption. Therefore tramadol can be administered without regard to food.
After repeated oral administration of 50 mg and 100 mg tramadol capsules at six hourly intervals, steady state is reached 30 to 36 hours after the first administration and the bioavailability is greater than 90%. The plasma concentrations at steady state exceeded by 52% and 36% those extrapolated from the single dose administration studies with 50 mg and 100 mg capsules respectively. This can be explained by first pass metabolic saturation.
After intramuscular injection of 50mg tramadol, the bioavailability is approximately 100%, and the peak serum level is attained after 45 minutes (range 50 to 90).
More than 90% of tramadol is absorbed after oral administration of Tramal® Retard. After a single dose, the mean absolute bioavailability is approximately 70%, irrespective of the concomitant intake of food. Oral bioavailability increases to 90% after repeated administration. The difference between absorbed and bioavailable tramadol is due to first-pass metabolism (maximum of 30%).
The administration of Tramal® Retard every 12 hours and Tramal® (immediate release) every 6 hours at the same daily dose, resulted in similar peak and trough serum tramadol concentrations and total tramadol exposure for the two preparations.
Serum tramadol concentrations in young males treated with Tramal® Retard (mean ± sd)
| Single Dose | Steady State | |||
|---|---|---|---|---|
| 100 mg | 200 mg | 100 mg q12 h | 200 mg q12 h | |
| Peak (ng/mL) | 142 ± 40 | 260 ± 113 | 293 ± 113 | 579 ± 149 |
| Time to peak (h) | 4.9 ± 0.8 | 4.8 ± 0.8 | 3.5 ± 1 | 3.9 ± 1.1 |
| Trough (ng/mL) | - | - | 156 ± 87 | 265 ± 67 |
Tramadol crosses the placental and blood-brain barriers. Very small amounts of tramadol and M1 are found in breast milk (0.1% and 0.02% respectively, of the administered dose).
Tramadol is extensively metabolised after oral administration. The major metabolic pathways appear to be N - and O -demethylation and glucuronidation or sulfation in the liver. Only O -desmethyltramadol (M1) is pharmacologically active. Production of M1 is dependent on the CYP2D6 isoenzyme of cytochrome P450. Patients who metabolise drugs poorly via CYP2D6 may obtain reduced benefit from tramadol, due to reduced formation of M1. N-demethylation is catalysed by the CYP3A4 isoenzyme of cytochrome P450.
The inhibition of one or both types of the isoenzymes CYP3A4 and CYP2D6 involved in the biotransformation of tramadol may affect the plasma concentration of tramadol or its active metabolite. Approximately 10% of the dose is excreted in the urine as unchanged drug, whereas 60% or more of the dose is excreted as metabolites.
Tramadol and its metabolites are excreted mainly by the kidneys, with a cumulative renal excretion (tramadol and metabolites) of approximately 95%. In young adults approximately 15 - 19% of an administered dose of tramadol is excreted in the urine as unmetabolised drug. In the elderly, this increases to about 35%. Biliary excretion is of little importance. In young adults, the half-life of tramadol is 5 - 7 h and the half-life of M1 is 6 - 8 h. Total clearance is approximately 430 - 610 mL/min.
Elimination of tramadol and M1 is impaired in patients with hepatic or renal impairment (see WARNINGS AND PRECAUTIONS). In patients with hepatic impairment, the mean half-life of tramadol was found to be 13 h (range up to 19 h ), and the mean half-life of M1 was 19 h (range up to 36 h). In patients with severe renal impairment (creatinine clearance < 5mL/min) the mean half-life of tramadol was 11 h (range up to 20 h), and the mean half life of M1 was 17 h (range up to 43 h).
In the elderly (age over 75 years), the volume of distribution of tramadol is decreased by 25% and clearance is decreased by 40%. As a result, tramadol Cmax and total exposure are increased by 30% and 50%, respectively, but the half-life of tramadol is only slightly prolonged (by 15%).
Relief of moderate to severe pain.
The dose of tramadol should be titrated to the severity of the pain and the clinical response of the individual patient.
The recommended dosage of tramadol in adults and adolescents over the age of 12 years is as follows:
Oral administration - for the treatment of moderate pain Tramal® 50 - 100 mg can be administered two or three times daily. Tramal® 50 mg may be adequate as the initial dose for moderate pain.
For moderate to severe pain, 50 - 100 mg as needed for relief, every four to six hours may be administered. Tramal® 100mg is usually more effective as the initial dose for more severe pain.
The maximum daily dose should not exceed 400mg per day.
Parenteral administration - Tramal® injection may be administered by intravenous injection, by intravenous infusion or intramuscularly. Intravenous injections should be given slowly over 2-3 minutes. For intravenous infusion, tramadol injection may be diluted in 0.9% sodium chloride, 5% glucose, 4.2% sodium bicarbonate, Ringer's solution, Ringer's lactate solution, Dextran 40 (10%) or polygeline 3.5%.
For postoperative pain, an initial bolus of 100 mg should be administered. During the 60 minutes following the bolus, further doses of 50 mg may be given every 10-20 minutes, to a total dose of 250 mg (including the bolus dose). Subsequent doses of 50mg or 100mg every four to six hours may be given, up to a total daily dose of 600 mg.
For less severe pain, 50 mg or 100 mg may be given every four to six hours to a maximum of 400 mg per day.
Oral administration - the recommended dose of Tramal® Retard in adults and adolescents over the age of 12 years is 100 mg to 200 mg twice daily, preferably morning and evening.
The tablets are to be taken whole, not divided or chewed, with sufficient liquid, irrespective of food intake.
The maximum daily dose should not exceed 400 mg per day.
Paediatric use - the use of tramadol is not recommended as safety and efficacy in children have not been established.
Use in the elderly - in subjects over the age of 75 years, serum concentrations are slightly elevated and the elimination half-life is slightly prolonged. The elderly can also be expected to vary more widely in their ability to tolerate adverse drug effects. Therefore, if necessary, the dosage interval is to be extended according to the patient's requirements. Changes in renal and/or hepatic function in the elderly may require adjustment of dose. See "Renal insufficiency" and "Hepatic insufficiency" for dose recommendations.
Renal insufficiency - impaired renal function results in a decreased rate and extent of excretion of tramadol and M1. In patients with creatinine clearances of less than 30 mL/min, adjustment of the dosage regimen is recommended. In these patients, the dosage interval of tramadol should be increased to 12 hours and Tramal® Retard should be increased to 24 hours. Since only 7% of an administered dose is removed by haemodialysis, dialysis patients can receive their regular dose on the day of dialysis.
Tramadol is not recommended in patients with severe renal impairment (creatinine clearance <10ml/min.).
Hepatic insufficiency - Tramal® Retard should not be used in patients with severe hepatic insufficiency. In these patients, the immediate release (IR) form of oral tramadol (capsule) may be administered if appropriate. In hepatic impairment, the initial oral dose of tramadol is 50 mg of the immediate release formulation. Depending on the severity of the impairment and individual clinical response, the recommended dosage interval (8 hours) may require to be extended, and/or the dose level titrated as required.
Tramadol is contraindicated in:
Tramadol must not be used for narcotic withdrawal treatment.
Tramal® Retard tablets contain 2.5 mg lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should consult a physician before use.
Tramadol should be administered cautiously in patients at risk of respiratory depression.
When large doses of tramadol are administered with anaesthetic medications or alcohol, respiratory depression may result. Cases of intra-operative respiratory depression, usually with large intravenous doses of tramadol and with concurrent administration of respiratory depressants, have been reported.
Tramadol should be used with caution in patients with increased intracranial pressure or head injury. Pupillary changes (miosis) from tramadol may obscure the existence, extent, or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating altered mental status in these patients if they are receiving tramadol.
The administration of tramadol may complicate the clinical assessment of patients with acute abdominal conditions.
Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, dosage reduction is recommended (see Dosage and Administration). Tramadol is not recommended in patients with severe renal impairment (creatinine clearance <10 mL/min.) (see Dosage and Administration). As tramadol is removed very slowly by haemodialysis or haemofiltration, post-dialysis administration to maintain analgesia is not usually necessary.
Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. In cirrhotic patients, dosage reduction is recommended (see Dosage and Administration).
With the prolonged half-life in these conditions, achievement of steady state is delayed, so that it may take several days for elevated plasma concentrations to develop.
Tramadol is not recommended as a substitute in opioid dependent patients. Although tramadol is an opiate-agonist, it cannot suppress opioid withdrawal symptoms. Animal experiments have shown that under certain circumstances the administration of tramadol may provoke a withdrawal syndrome in opioid-dependent monkeys.
Because of the difficulty in assessing dependence in patients who have previously received substantial amounts of opioid medications, caution should therefore be used in the administration of tramadol to such patients.
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.
Cases of dependence and abuse of tramadol have been reported rarely.
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 medication that lowers the seizure threshold (see Interactions). Patients with epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling circumstances.
Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving tramadol. These reactions often occur following the first dose. Other reported reactions include pruritus, hives, bronchospasm and angioedema.
In one study using nitrous oxide/tramadol anaesthetic technique (with only intermittent administration of enflurane "as required"), tramadol was reported to enhance intraoperative recall. Hence its use during potentially very light levels of general anaesthesia should be avoided.
Two recent studies of tramadol administration during anaesthesia comprising continuous administration of isoflurane did not show clinical lightening of anaesthetic depth or intraoperative recall. Therefore, providing the current practice of administering continuous, potent (volatile or intravenous) anaesthetic agent is followed, tramadol may be used intraoperatively in the same way as other analgesic agents are routinely used.
Tramadol has been studied in controlled clinical trials for periods of up to three months. In one small uncontrolled study, patients with cancer pain received a dose of 150 mg tramadol per day for up to six months. Beyond six months no clinical studies investigating the safety and efficacy of tramadol are available.
When tramadol treatment of pain is required long-term, careful and regular monitoring should be carried out to establish whether and to what extent ongoing treatment is necessary.
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 hamster cells, and bone marrow micronucleus tests in mice and Chinese hamster cells. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus tests in rats. Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans.
A slight, but statistically significant increase in two common murine tumours, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice (dosing orally up to 30 mg/kg for approximately two years, although the study was not done with the Maximum Tolerated Dose or at exposure levels expected in clinical use), this finding is not believed to suggest risk in humans. No such finding occurred in a rat carcinogenicity study.
No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male rats and 75mg/kg in female rats.
Tramadol is Pregnancy Category C. There are no adequate and well-controlled studies with tramadol in pregnant women. Tramadol should be used during pregnancy only if the potential benefit outweighs the potential risk to the foetus because safe use in pregnancy has not been established.
Tramadol has been shown to be embryotoxic and foetotoxic in mice, rats and rabbits in maternally toxic doses 3 to 15 times the maximum human dose or higher (120 mg/kg in mice, 25 mg/kg or higher in rats and 75 mg/kg or higher in rabbits), but was not teratogenic at these dose levels. No harm to the foetus due to tramadol was seen at doses that were not maternally toxic.
No drug-related teratogenic effects were observed in progeny of mice, rats or rabbits treated with tramadol by various routes (up to 140 mg/kg for mice, 80 mg/kg for rats or 300 mg/kg for rabbits). Embryo and foetal toxicity consisted primarily of decreased foetal weights, skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. Transient delays in development or behavioural parameters were also seen in pups from rat dams allowed to deliver. Embryo and foetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit.
In peri- and post-natal studies in rats, progeny of dams receiving oral (gavage) dose levels of 50 mg/kg or greater had decreased weights and pup survival was decreased early in lactation at 80 mg/kg (6-10 times the maximum human dose). No toxicity was observed for progeny of dams receiving 8, 10, 20, 25 or 40 mg/kg. Maternal toxicity was observed at all dose levels, but effects on progeny were evident only at higher dose levels where maternal toxicity was more severe.
Tramadol is not recommended for obstetric preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Low levels of tramadol have been detected in breast milk. Following a single intravenous 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post-dose was 100 µg of tramadol (0.1% of the maternal dose) and 27 µg of M1.
Tramadol should not be used in pregnant women prior to or during labour unless the potential benefits outweigh the potential risks, because safe use in pregnancy has not been established. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labour.
The effect of tramadol, if any, on the later growth, development, and functional maturation of the child is unknown.
Tramadol may cause sedation. Use caution if intending to drive or operate machinery.
Adverse reactions that may occur after administration of tramadol resemble those known to occur with opioids. Adverse reactions were recorded in 13,802 patients from trials with different formulations of tramadol. The nature and incidence of reactions (in CIOMS format where very common = > 1/10;
common = 1/100 and <1/10; uncommon = 1/1000 and <1/100; rare = 1/10,000 and <1/1000; and very rare = < 1/10,000) were as follows:
| Uncommon: | orthostatic dysregulation (tendency to collapse, and cardiovascular collapse) and tachycardia. |
| Rare: | increase in blood pressure, bradycardia |
| Very rare: | worsening of asthma (causality not established), respiratory depression (when the recommended doses are considerably exceeded and other respiratory depressant substances are administered concomitantly) |
| Very common: | nausea |
| Common: | constipation |
| Uncommon: | dyspepsia, diarrhoea, abdominal pain, flatulence, urge to vomit |
| Rare: | changes in appetite |
| Very rare: | increase in liver enzyme values |
| Very common: | dizziness |
| Common: | autonomic nervous effects (mainly dry mouth, perspiration), sedation, headache, asthenia, fatigue |
| Uncommon: | trembling |
| Rare: | elevated mood, sensory effects, hallucinations, confusion, coordination disturbance, sleep disturbance, nightmares, motor system weakness, changes in appetite, tremor, respiratory depression, seizures |
| Common: | sweating |
| Uncommon: | skin reactions, pruritus, rash |
| Rare: | shock reactions, anaphylaxis, allergic reactions |
| Rare: | micturition disorders (difficulty in passing urine and urinary retention) |
| Rare: | visual disturbance (blurred vision) |
The incidence of "non-specific CNS irritation" (dizziness),
"autonomic nervous effects" (perspiration), "orthostatic
dysregulation (tendency to collapse and cardiovascular collapse) and tachycardia
"and "nausea/urge to vomit/vomiting" can be increased with rapid
intravenous administration and also tends to be dose dependent. No tests of
significance have been performed.
Although tramadol can produce drug dependence of the µ-opioid type (like codeine or dextropropoxyphene) and potentially may be abused, there has been little evidence of abuse in clinical experience to date. In clinical trials, tramadol produced some effects similar to an opioid, and at supratherapeutic doses was recognised as an opioid in subjective/behavioural studies. Tolerance development has been reported to be relatively mild and withdrawal, when present, is not considered to be as severe as that produced by other opioids. Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal, may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor, and gastrointestinal symptoms. Part of the activity of tramadol is thought to be derived from its active metabolite, which is responsible for some delay in onset of activity and some extension of the duration of µ-opioid activity. Delayed µ-opioid activity is believed to reduce a drug's abuse potential.
Tramadol should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anaesthetic agents, phenothiazines, tranquillisers or sedative hypnotics.
The combination of tramadol with mixed opiate agonists/antagonists (eg. buprenorphine, pentazocine) is not advisable because the analgesic effect of a pure agonist may theoretically be reduced in such circumstances.
Tramadol can induce convulsions and increase the potential for selective serotonin re-uptake inhibitors, tricyclic antidepressants, antipsychotics and other seizure threshold lowering agents to cause convulsions.
The presence of another drug that increases serotonin by any mechanism should alert the treating physician to the possibility of an interaction. In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tramadol in combination with other serotonergic medicines such as selective serotonin reuptake inhibitors (SSRIs). Signs of serotonin syndrome may be, for example, confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus and diarrhoea. Withdrawal of the serotonergic medicines usually brings about a rapid improvement. Drug treatment depends on the nature and severity of the symptoms.
Caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (eg. Warfarin) due to reports of increased international normalised ratio (INR) and ecchymoses in some patients.
Tramadol should not be used in patients who are taking MAO inhibitors or who have taken them within the last fourteen days since tramadol inhibits the uptake of noradrenaline and serotonin.
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.
Concomitant administration of tramadol with carbamazepine causes a significant increase in tramadol metabolism, presumably through metabolic induction by carbamazepine. Patients receiving chronic carbamazepine doses of up to 800 mg daily may require up to twice the recommended dose of tramadol.
Tramadol is metabolised to M1 by the CYP2D6 P450 isoenzyme. Drugs that selectively inhibit that isoenzyme (quinidine, phenothiazines, antipsychotic agents) may cause increased concentrations of tramadol and decreased concentrations of M1. The clinical consequences of this effect have not been fully investigated.
Concomitant administration of tramadol with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore no alteration of the tramadol dosage regimen is recommended.
Other drugs known to inhibit the CYP3A4 isoenzyme of cytochrome P450, such as ketoconazole and erythromycin, may inhibit the metabolism (via N-demethylation) of tramadol and probably the metabolism of M1. The clinical importance of such an interaction has not been studied.
Few cases of overdose with tramadol have been reported.
Serious potential consequences of overdosage are respiratory depression and seizure. Naloxone will reverse respiratory depression but not all symptoms caused by overdosage with tramadol, so that general supportive treatment is recommended. Adequate ventilation should be maintained. Haemodialysis is not expected to be helpful because it removes only a small percentage of the administered dose. Convulsions occurring in mice following the administration of toxic doses of tramadol could be suppressed with barbiturates or benzodiazepines, but were increased with naloxone. Naloxone did not change the lethality of an overdose in mice.
Tramal® solution for injection is incompatible with injection solutions containing diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, glyceryl trinitrate or midazolam.
Tramal® solution for injection is compatible with the following intravenous fluids: 0.9% sodium chloride, 5% glucose, 4.2% sodium bicarbonate, Ringer's solution, Ringer's lactate solution, Dextran 40 (10%) or polygeline 3.5%.
Tramal® 50 solution for injection, Tramal® 100 solution for injection and Tramal® capsules 50mg should be stored below 30oC.
Prescription-only Medicine
Tramal® 50mg immediate release capsules-packs of 6, 10, 20, 30 and 50 capsules.
Tramal® 50, solution for injection-pack containing 5 ampoules of 1 mL each.
Tramal® 100, solution for injection-pack containing 5 ampoules of 2 mL each.
Tramal® Retard 100 mg, 150 mg and 200 mg sustained release tablets - packs of 10 and 30 tablets.
Tramal® preparations contain tramadol hydrochloride known chemically as (±)-cis-2-(dimethylaminomethyl)-1-(3-methoxyphenyl)-cyclohexanol hydrochloride. It is an odourless, white to off-white crystalline powder that is readily soluble in both water and ethanol and has a pKa of 9.41. The water/n-octanol partition coefficient is 1.35 at pH 7. It belongs to the class of synthetic analgesics and has opioid-like activity, with the formula: C16 H25 NO2. HCl. MW = 299.84.
The structural formula of tramadol hydrochloride is:-
The CAS Registry Number is 36282-47-0
CSL (New Zealand) Limited
666 Great South Road
Penrose, Auckland 6
New Zealand
December 2002
Tramal® is a registered trademark of Grunenthal GmbH used by CSL Limited as authorised user.
