Consumer medicine information

Tramadol AN SR Tablets

Tramadol hydrochloride


Brand name

Tramadol AN SR Tablets

Active ingredient

Tramadol hydrochloride




Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tramadol AN SR Tablets.

What is in this leaflet

This leaflet answers some common questions about this medicine.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given TRAMADOL AN SR against the benefits it is expected to have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What TRAMADOL AN SR is used for

TRAMADOL AN SR is used to relieve moderate to severe pain. It belongs to the group of medicines called analgesics (pain relievers). TRAMADOL AN SR tablets are designed to release the active ingredient for pain relief gradually over several hours.

Before you use TRAMADOL AN SR for the first time

Tell your doctor if:

  • you are allergic to any of the ingredients in TRAMADOL AN SR (see "Product Description”)
  • you are known to be sensitive to opioids
  • you have lung or breathing problems
  • you are taking any medicines for depression, or mental or psychiatric disorder or to help you sleep
  • you are taking medication known as selective serotonin reuptake inhibitors (SSRI's), tricyclic anti-depressants, quinidine, phenothiazines or anti psychotics
  • you have had any fits or convulsions, or take medicines for epilepsy
  • you are taking the medicine carbamazepine (one Brand name is Tegretol)
  • you have any disorder of the kidney, liver or pancreas, including any related to alcohol intake - for example, cirrhosis of the liver
  • you have a stomach problem
  • you have a severe headache or have had a head injury
  • you have, or have had, any drug or alcohol dependence
  • you are taking any other medicine, including those you buy from a pharmacy or supermarket

Use in children

TRAMADOL AN SR is not recommended for children under 12 years.

Use in the elderly

Patients over 75 years may need a reduced daily dose of TRAMADOL AN SR compared to younger adults.

If you are pregnant or intend to become pregnant:

TRAMADOL AN SR is not recommended for use during pregnancy. Talk to your doctor about the risks and benefits of using TRAMADOL AN SR during pregnancy.

If you are breast-feeding or plan to breast feed:

TRAMADOL AN SR is not recommended for use during breast-feeding. Talk to your doctor about the risks and benefits using TRAMADOL AN SR when breast-feeding.

If you are driving or operating machinery

TRAMADOL AN SR may make you drowsy or dizzy. Ask your doctor or pharmacist for advice about whether it is safe for you to drive or operate machinery while taking TRAMADOL AN SR.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines may interfere with TRAMADOL AN SR. These include:

  • carbamazepine (eg. Tegretol)
  • coumarin derivatives (eg. Warfarin: some Brand names are Coumadin or Marevan)
  • ondansetron
  • medicine for irregular or rapid heart beat
  • medicines for depression, sleeplessness or mental conditions such as selective serotonin reuptake inhibitors (SSRI's), tricyclic anti-depressants, quinidine, phenothiazines or anti-psychotics
  • some antibiotics.

These medicines may be affected by TRAMADOL AN SR, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Other interactions not listed above may also occur.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking TRAMADOL AN SR

How Tramadol AN should not be used

You should NOT use TRAMADOL AN SR if:

  • you have an allergy to any of the ingredients (see “Product Description” for details)
  • you have an allergy to any other medicines known as opioid analgesics, eg. morphine or codeine.
  • you have taken large amounts of alcohol or other substances which can affect your level of consciousness
  • you are taking medicine for depression containing a "monoamine oxidase inhibitor" also known as MAOI, or have taken any within the past two weeks. Examples of MAOI-containing medicines are Nardil, Parnate.
  • you are having treatment for withdrawal from narcotics
  • the packaging is torn or shows signs of tampering
  • any tablets look damaged or discoloured
  • it is after the expiry date which is printed on the carton.

How Tramadol AN is used

TRAMADOL AN SR tablets should be swallowed whole with water. They may be taken before, with, or after food.

They must NOT be chewed, crushed or dissolved. This will release all active ingredient for pain relief quite quickly. Side effects may then occur.

The recommended dosage of TRAMADOL AN SR is either:

  • one or two TRAMADOL AN SR 100 mg tablet(s) twice a day (morning and evening)
  • one TRAMADOL AN SR 150 mg or 200 mg tablet twice a day (morning and evening).

Do not take more than four of the 100 mg tablets per day.

Do not take more than two of the 150 mg or of the 200 mg tablets per day.

What to do if you have missed your dose

If you forget to take one dose, take the dose when you remember. The following dose should be taken after twelve hours, or as prescribed by your doctor.

How long you should take TRAMADOL AN SR

This varied from individual to individual. It depends, for example, on how severe your pain is, how you respond to TRAMADOL AN SR, and the cause of your pain. Ask your doctor for advice on how long you need to take TRAMADOL AN SR tablets.

As with all medicines:

  • take only as your doctor has told you.
  • if you feel that you do not need as much TRAMADOL AN SR as your doctor has prescribed for you, talk to your doctor.
  • tell your doctor if your pain is not helped or gets worse. Do not take increased amounts or extra doses of TRAMADOL AN SR unless your doctor advises you to.

Side effects of TRAMADOL AN SR

All medicines can cause unwanted effects, and some side effects have been reported with TRAMADOL AN SR. Side effects reported with TRAMADOL AN SR are usually minor and temporary, but some may be serious.

The most common side-effects of TRAMADOL AN SR are:

  • dizziness
  • sedation, fatigue
  • headache
  • constipation
  • nausea, vomiting
  • sweating
  • dry mouth.

The following side-effects are less common:

  • indigestion
  • changes in appetite
  • skin reactions
  • sudden onset of low blood pressure, collapse
  • muscle weakness
  • tremor
  • seizures
  • respiratory depression
  • improvement of mood
  • confusion
  • sleep disturbance
  • blurred vision
  • difficulty in passing urine
  • Serotonin Syndrome: signs of this vary and are not specific. They may include fever, sweating, confusion, agitation, diarrhoea, muscle twitching, difficulty with walking and balance. Serotonin Syndrome may result from interaction of tramadol with other medicines which increase serotonin effects, for example, the SSRI antidepressants.

This is not a complete listing. Occasionally, other side effects may be experienced.

Tell your doctor immediately if you experience any of the following side effects, as urgent medical treatment may be required:

  • skin rash (red spots or patches), itching hives, skin lumps
  • swelling or puffiness of the eyelids, face or lips
  • chest tightness, wheezing or pain in the chest
  • heart palpitations, faintness or collapse
  • hallucinations
  • convulsions

If you experience any side-effects that have not been mentioned here, consult your doctor or pharmacist as soon as possible.

You should remember that all medicines carry some risks. It is possible that some risks might not yet have been detected despite many years of experience with the medicine.

Is TRAMADOL AN SR addictive

When used as prescribed by your doctor, addiction to TRAMADOL AN SR is very unlikely.

If you are taking TRAMADOL AN SR for a prolonged period of time, your body may become used to the medicine and mild withdrawal symptoms may occur if you suddenly stop taking the medicine.

It is important therefore to take TRAMADOL AN SR only as directed by your doctor.

What to do in the case of overdosage

In the event of overdose, you should contact your nearest Poisons Information Centre (phone: 131 126), doctor or hospital emergency department immediately.

Overdosage with TRAMADOL AN SR will result in a decrease in breathing and fits or convulsions.


  • Keep TRAMADOL AN SR in a safe place, where children cannot reach it.
  • Store in a cool, dry place, below 25ºC.
  • Keep away from direct sunlight.
  • Do not use TRAMADOL AN SR after the use-by-date printed on the carton.

Product description

What it looks like

  • TRAMADOL AN SR 100 mg - off-white, round biconvex tablet
  • TRAMADOL AN SR 150 mg - off-white, capsule shaped tablet
  • TRAMADOL AN SR 200 mg - off-white, capsule shaped tablet

All tablets are contained in a blister pack within a carton.


Active ingredient:

  • Tramadol hydrochloride

Inactive ingredients:

  • Calcium hydrogen phosphate
  • Hydroxypropylcellulose
  • Silica - colloidal anhydrous
  • Magnesium stearate


Southern Cross Pharma Pty Ltd
56 Illabunda Drive
Malua Bay
NSW 2536

Date of Information:

May 2014

AUST R Number
TRAMADOL AN SR 100 mg: AUST R 190051
TRAMADOL AN SR 150 mg: AUST R 190052
TRAMADOL AN SR 200 mg: AUST R 190053


Brand name

Tramadol AN SR Tablets

Active ingredient

Tramadol hydrochloride




Name of the medicine

Tramadol hydrochloride.


Calcium hydrogen phosphate, hyprolose, anhydrous colloidal silica and magnesium stearate.


Chemical name: (1RS,2RS)-2-[(dimethylamino)methyl)]-1-(3-methoxyphenyl)cyclohexanol hydrochloride. Molecular formula: C16H25NO2.HCl. MW: 299.84. CAS: 53611-16-8. Tramadol hydrochloride is an odourless, white to off white crystalline powder that is readily soluble in both water and ethanol. The water/n-octanol partition coefficient is 1.35 at pH 7.


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 the mode of action is not completely understood, at least two complementary mechanisms appear applicable: binding to mu-opioid receptors and inhibition of reuptake of noradrenaline and serotonin. The opioid-like activity of tramadol derives from low affinity binding of the parent compound to mu-opioid receptors and higher affinity binding of the principal active metabolite, mono O-desmethyltramadol, denoted M1, to mu-opioid receptors. In animal models, M1 is up to six times more potent than tramadol in producing analgesia and 200 times more potent in mu-opioid binding. The contribution of tramadol to human analgesia, relative to M1, is unknown.
Both human and animal 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 dependent, 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 postoperative analgesia was 300 nanogram/mL, with individual values ranging from 20 to 990 nanogram/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.


After oral administration of tramadol modified release tablets, more than 90% of tramadol is absorbed. 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 30%). See Table 1.


Tramadol is rapidly distributed in the body, with a volume of distribution of 2 to 3 L/kg in young adults. The volume of distribution is reduced by about 25% in those aged over 75 years. Plasma protein binding is about 20% and is independent of concentration up to 10 microgram/mL. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range.
Tramadol crosses both the placenta and the blood brain barrier. 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.


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 to 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 five to seven hours and the half-life of M1 is six to eight hours. Total clearance is approximately 430 to 610 mL/minute.

Pharmacokinetics in patients with hepatic or renal impairment.

Elimination of tramadol and M1 is impaired in patients with hepatic or renal impairment (see Precautions). In patients with hepatic impairment, the mean half-life of tramadol was found to be 13 hours (range up to 19 hours), and the mean half-life of M1 was 19 hours (range up to 36 hours). In patients with severe renal impairment (creatinine clearance < 5 mL/minute) the mean half-life of tramadol was eleven hours (range up to 20 hours), and the mean half-life of M1 was 17 hours (range up to 43 hours).

Pharmacokinetics in the elderly.

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.


Individuals with known hypersensitivity to tramadol or any excipients.
Acute intoxication with alcohol, hypnotics, analgesics, opioids or psychotropic drugs.
Patients who are receiving monoamine oxidase (MAO) inhibitors or who have taken them within the last 14 days.
Known sensitivity to opioids.
Patients with uncontrolled epilepsy or epilepsy not adequately controlled by treatment.
Tramadol must not be used for narcotic withdrawal treatment.


Acute abdominal conditions.

The administration of tramadol may complicate the clinical assessment of patients with acute abdominal conditions.

Respiratory depression.

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 intraoperative respiratory depression, usually with large intravenous doses of tramadol and with concurrent administration of respiratory depressants, have been reported.

Increased intracranial pressure, head trauma, shock or reduced levels of consciousness.

Tramadol should be used with caution in patients with increased intracranial pressure, head injury, shock or a reduced level of consciousness of uncertain origin. 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.

Patients physically dependent on opioids.

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 for 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.

Seizure risk.

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. In addition, tramadol may increase the seizure risk in patients taking other medications that lower the seizure threshold (see Interactions with Other Medicines). Patients with epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling circumstances.

Anaphylactoid reactions.

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.

Intraoperative use.

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 planes of general anaesthesia should be avoided. Two recent studies of tramadol administration during anaesthesia comprising continuous administration of isoflurane did not show clinically significant 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.

Long-term use.

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 tramadol 150 mg/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.

Renal and hepatic disease.

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. (See Impaired renal function and Impaired hepatic function, below.)

Impaired renal function.

In patients with renal 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. In cases of severe renal insufficiency tramadol prolonged release tablets are not recommended.
As tramadol is only removed very slowly by haemodialysis or haemofiltration, postdialysis administration to maintain analgesia is not usually necessary.

Impaired hepatic function.

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).

Effects on fertility.

No effects on fertility in rats were observed for tramadol at oral dose levels of up to 50 mg/kg/day.

Use in pregnancy.

(Category C)
There are no adequate and well controlled studies with tramadol in pregnant women, therefore tramadol should not be used during pregnancy. Studies in animals using intravenous or intramuscular routes of administration have not been conducted.
Tramadol has been shown to be embryotoxic and fetotoxic in mice, rats and rabbits at maternally toxic doses of 120 mg/kg in mice, or higher in rats and 75 mg/kg in rabbits, but was not teratogenic at these dose levels. No harm to the fetus 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 (75 mg/kg for rats or 175 mg/kg for rabbits). Embryo and fetal toxicity consisted primarily of decreased fetal 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 fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit.
In perinatal and postnatal studies in rats, progeny of dams receiving oral (gavage) dose levels of 50 mg/kg had decreased weights and pup survival was decreased early in lactation at 80 mg/kg (six to ten 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.

Labour and delivery.

Tramadol should not be used in pregnant women prior to or during labour unless the potential benefits outweigh the risks, because safe use in pregnancy has not been established. If tramadol were to be used during labour, it may cause respiratory depression in the newborn infant. 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.

Use in lactation.

Tramadol is not recommended during breastfeeding, 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 dose of tramadol 100 mg, the cumulative excretion in breast milk within 16 hours postdose was tramadol 100 microgram (0.1% of the maternal dose) and M1 27 microgram.

Use in children.

The use of tramadol is not recommended as safety and efficacy in children 12 years and under 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. Patients in this age group are also expected to vary more widely in their ability to tolerate adverse drug effects. Daily doses in excess of 300 mg are not recommended in patients over 75 years.


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 dosed orally up to 30 mg/kg for approximately two years. Although the study was not conducted using the maximum tolerated dose or at exposure levels expected in clinical use, this finding is not believed to suggest risk in humans. No such findings occurred in a rat carcinogenicity study.


Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the presence of metabolic activation), dominant lethal mutation tests in mice, chromosome aberration tests in Chinese hamster cells and bone marrow micronucleus tests in mouse and Chinese hamster cells. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and the micronucleus tests in rat cells. Overall, the weight of evidence from these tests indicates tramadol does not possess a genotoxic risk to humans.

Effect on ability to drive or operate machinery.

Due to its sedative effect, patients should be advised to avoid driving or operating heavy machinery while taking tramadol.


Central nervous system depressants.

Tramadol should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anaesthetic agents, phenothiazines, tranquillizers or sedative hypnotics.
The combination of tramadol with mixed opiate agonists/ antagonists (e.g. buprenorphine or pentazocine) is not advisable because the analgesic effect of a pure agonist may be theoretically reduced in such circumstances.

Use with other serotonergic agents.

The presence of another drug that increases serotonin by any mechanism should alert the treating doctor to the possibility of an interaction.
Concomitant therapeutic use of tramadol and serotonergic medicines such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors (see Contraindications), tricyclic antidepressants and mirtazapine may cause serotonin toxicity. 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 > 38°C and inducible or ocular clonus.
Withdrawal of the serotonergic medicines usually brings about a rapid improvement. Drug treatment depends on the nature and severity of the symptoms.

Use with coumarin derivatives.

Caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (e.g. warfarin) due to reports of increased international normalised ratio (INR) with major bleeding and ecchymoses in some patients.

Drugs which reduce the seizure threshold.

Tramadol can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other seizure threshold lowering drugs (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions.

Use with monoamine oxidase inhibitors.

Tramadol should not be used in patients who are taking MAOIs or who have taken them within the last 14 days, as tramadol inhibits the uptake of noradrenaline and serotonin (see Contraindications).

Other interactions.

Tramadol does not appear to induce its own metabolism in humans, since observed maximal serum 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 isoenzyme. Drugs that selectively inhibit that isoenzyme (quinidine, phenothiazines and antipsychotic agents) may cause increased concentrations of tramadol and decreased concentrations of M1. The clinical consequences of these potential effects 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, such as ketoconazole and erythromycin, may inhibit the metabolism of tramadol (via N-demethylation) and probably the metabolism of the active O-demethylated metabolite (M1). The clinical importance of such an interaction has not been studied.
In a limited number of studies, the preoperative or postoperative application of the antiemetic 5-HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.

Adverse Effects

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 (greater than or equal to 1/10); common (greater than or equal to 1/100 and < 1/10); uncommon (greater than or equal to 1/1,000 and < 1/100); rare (greater than or equal to 1/10,000 and < 1/1,000); and very rare (less than 1/10,000) were as follows.

Immune system disorders.

Rare: shock reactions, anaphylaxis, allergic reactions.

Endocrine disorders.

Very rare: syndrome of inappropriate antidiuretic hormone secretion characterised by hyponatraemia secondary to decreased freewater excretion.

Metabolism and nutrition disorders.

Rare: changes in appetite.

Psychiatric disorders.

Rare: hallucinations, confusional state, sleep disturbance, delirium, anxiety, nightmares, changes in mood (usually euphoric mood, occasionally dysphoria), changes in activity (usually suppression, occasionally increase), changes in cognitive and sensorial capacity (e.g. decision behaviour, perception disorders).

Nervous system disorders.

Very common: dizziness. Common: autonomic nervous effects (mainly dry mouth, perspiration), headache, sedation, asthenia. Uncommon: trembling. Rare: speech disorders, paraesthesia, coordination disturbance, tremor, seizures, involuntary muscle contractions, syncope.

Eye disorders.

Rare: miosis, mydriasis, visual disturbance (blurred vision).

Cardiac disorders.

Uncommon: tachycardia, flushing. Rare: bradycardia.

Vascular disorders.

Uncommon: orthostatic dysregulation (tendency to collapse and cardiovascular collapse).

Respiratory, thoracic and mediastinal disorders.

Rare: dyspnea, respiratory depression (when the recommended doses are considerably exceeded and other respiratory depressant substances are administered concomitantly). Very rare: worsening of asthma (causality not established).

Gastrointestinal disorders.

Very common: nausea. Common: vomiting, constipation. Uncommon: dyspepsia, diarrhoea, abdominal pain, flatulence, urge to vomit.

Hepatobiliary disorders.

Very rare: elevated liver enzymes.

Skin and subcutaneous tissue disorders.

Common: sweating. Uncommon: skin reactions, pruritus, rash.

Musculoskeletal and connective tissue disorders.

Rare: motor system weakness.

Renal and urinary disorders.

Rare: micturition disorders (difficulty in passing urine and urinary retention), dysuria.

General disorders and administration site conditions.

Common: fatigue.


Rare: increase in blood pressure.
The incidence of “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.

Drug abuse and dependence.

Although tramadol can produce drug dependence of the mu-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. 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 mu-opioid activity. Delayed mu-opioid activity is believed to reduce a drug's abuse liability.

Tolerance and withdrawal.

Tolerance development has been reported to be relatively mild. Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal, may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor, pyrexia, myalgia, chills and gastrointestinal symptoms. Other symptoms that have very rarely been seen with tramadol discontinuation include panic attacks, severe anxiety, hallucinations, paraesthesiae, tinnitus and unusual CNS symptoms (i.e. confusion, delusions, depersonalisation, derealisation, paranoia).

Dosage and Administration

The dose of tramadol should be titrated according to the severity of the pain and the clinical response of the individual patient. Tramadol is approved for use in adults and adolescents over the age of 12 years.

Tramadol AN SR tablets.

The recommended dose of Tramadol AN SR in adults and adolescents over the age of 12 years is 100 to 200 mg twice daily, preferably morning and evening. For initial titration therapy, a lower starting dose may be appropriate for some patients. 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 SR is not recommended as safety and efficacy in children over the age of 12 years have not been established.

Dosage in the elderly.

In subjects over the age of 75 years, serum concentrations are slightly elevated and the elimination half-life is slightly prolonged. Subjects in this age group are also expected to vary more widely in their ability to tolerate adverse drug effects. Daily doses in excess of 300 mg are not recommended in patients over 75 years.

Renal insufficiency.

In patients with renal 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. In cases of severe renal insufficiency Tramadol SR prolonged release tablets are not recommended.
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 < 10 mL/minute).

Hepatic insufficiency.

Tramadol AN SR should not be used in patients with severe hepatic insufficiency.


Few cases of overdose with tramadol have been reported.


Symptoms of overdosage with tramadol are similar to those of other centrally acting analgesics (opioids) and include miosis, vomiting, cardiovascular collapse, consciousness disorders including coma, convulsions, respiratory depression and respiratory arrest.


Should overdosage occur, general emergency measures should be implemented. Keep the respiratory airways open and maintain respiration and circulation. If overdosage is due to ingestion of a sustained release oral dose form of tramadol, emptying the stomach by gastric lavage should be considered because of the possibility of ongoing release in the stomach. Activated charcoal may reduce absorption of the drug if given within one to two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Naloxone will reverse respiratory depression, but not all symptoms caused by overdosage with tramadol. 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.
Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore, treatment of overdosage with tramadol with haemodialysis or haemofiltration alone is not suitable for detoxification.
Contact the Poisons Information Centre on 131 126 for advice on the management of overdose.


Modified release tablets (off white), 100 mg (round, biconvex), 150 mg (capsule shaped), 200 mg (capsule shaped): 20's (PVC/Al blister pack in carton).


Store below 25°C. Protect from light and moisture.

Poison Schedule