Consumer medicine information

Terry White Chemists Tramadol

Tramadol hydrochloride


Brand name

Terry White Chemists Tramadol

Active ingredient

Tramadol hydrochloride




Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Terry White Chemists Tramadol.

What is in this leaflet

Read this leaflet carefully before taking your medicine. This leaflet answers some common questions about tramadol. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is Terry White Chemists Tramadol. It contains the active ingredient tramadol hydrochloride.

It is used to treat:

  • moderate to severe pain

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

Tramadol is not normally addictive, although some cases have been reported.

Use in children

This medicine should not be used in children. The safety and effectiveness of this medicine in children have not been established.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You have or have had any of the following:
    - epilepsy which is not well controlled
    - known sensitivity to opioids (such as morphine or codeine).
  • You are taking a class of medicine known as 'monoamine oxidase inhibitors' (MAOIs) (often taken for depression), or you have taken such a medicine within the last 14 days.
  • You have recently taken large amounts of alcohol, hypnotics (often used to treat insomnia), analgesics (painkillers), opioids (also often used to treat pain), or psychotropic drugs (affect brain function)
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.
  • You are hypersensitive to, or have had an allergic reaction to, tramadol or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body, rash, itching or hives on the skin; fainting or hayfever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.

Before you start to take it

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • lung or breathing problems
  • serious head injury, shock or reduced levels of consciousness
  • diseases of the kidney or liver
  • acute abdominal or stomach problems
  • seizures, fits or convulsions/epilepsy
  • dependence on opioid medications(such as morphine or codeine).
  1. You are currently pregnant or you plan to become pregnant. Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.
  2. You are currently breast-feeding or you plan to breast-feed. Do not take this medicine whilst breast-feeding until you and your doctor have discussed the risks and benefits involved.
  3. You are planning to have surgery or an anaesthetic.
  4. You are currently receiving or are planning to receive dental treatment.
  5. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines may interact with tramadol. These include:

  • certain medicines used to treat depression, sleeplessness or mental conditions (such as MAOIs, selective serotonin reuptake inhibitors (SSRIs), tricyclic anti-depressants, phenothiazines or anti-psychotics)
  • CNS depressants (such as alcohol, opioids, tranquilisers or sedative hypnotics)
  • carbamazepine, a medicine mainly used to treat epilepsy
  • coumarin derivatives (such as warfarin)
  • ondansetron, a medicine used to treat nausea and vomiting.

If you are taking any of these you may need a different dose or you may need to take different medicines.

Other medicines not listed above may also interact with tramadol.

How to take this medicine

Follow carefully all directions given to you by your doctor or pharmacist. Their instructions may be different to the information in this leaflet.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

For moderate pain:
The usual adult dose is one or two capsules taken two or three times daily.
One capsule (50 mg) may be enough for the first dose.

For moderate to severe pain:
The usual adult dose is one or two capsules, every four to six hours.
Two capsules (100 mg) are usually required for the first dose.

Do not take more than eight capsules (400 mg) per day.

If you are over 75 years of age, do not take more than six capsules (300 mg) per day, as you may require a lower daily dose.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

How to take it

Follow all directions given to you by your doctor or pharmacist carefully.

They may be different to the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

When to take it

Take this medicine at the same time each day. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

It does not matter if you take it before, with or after food.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose, skip the missed dose and take your next dose at the usual time. Otherwise take it as soon as you remember and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for missed doses. This may increase the chance of you experiencing side effects.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints to help you remember.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively go to the Accident and Emergency Department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking this medicine

Things you must do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breast-feeding or are planning to breast-feed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects. Go to your doctor regularly for a check-up.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours
  • Take your medicine to treat any other condition unless your doctor or pharmacist tells you to
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking tramadol or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor or pharmacist if you notice any of the following.

Mostly, these are mild:

  • dizziness
  • drowsiness
  • dry mouth
  • headache
  • physical weakness or loss of strength
  • fatigue
  • nausea or vomiting
  • constipation
  • indigestion and stomach pain
  • flatulence.

Tell your doctor as soon as possible if you notice any of the following.

These may be serious side effects. You may need medical attention.

  • itchy skin/rash
  • sudden onset of low blood pressure; collapse
  • fast heart beat
  • hot flushes
  • tremors/shakes
  • increase in blood pressure
  • slow heart beat
  • shortness of breath
  • changes in appetite
  • changes in mood
  • sleep disturbances
  • muscle weakness
  • difficulty in breathing
  • difficulty or pain in passing urine
  • blurred vision
  • problems with speech
  • dilated pupils.

If you experience any of the following, stop taking your medicine and contact your doctor immediately or go to the Accident and Emergency department at your nearest hospital. These are very serious side effects. You may need urgent medical attention or hospitalisation.

  • Serotonin Syndrome: symptoms of which may vary and are not specific, they may include: fever, sweating, confusion, agitation, diarrhoea, muscle twitching, difficulty with walking and balance
  • hallucinations
  • seizures

Other side effects not listed above may occur in some patients.

Some patients may experience withdrawal symptoms after they stop taking this medicine, such as agitation, trouble sleeping or tremors. Tell your doctor if you experience withdrawal symptoms.

Allergic reactions

If you think you are having an allergic reaction to tramadol, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • cough, shortness of breath or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hayfever-like symptoms.

Storage and disposal


Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.


If your doctor or pharmacist tells you to stop taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What Terry White Chemists Tramadol looks like

The capsules have a green cap and yellow body and are filled with a homogeneous white to off-white powder.

They are available in blister packs of 20 capsules.

* Not all strengths, pack types and/or pack sizes may be available.


Each capsule contains 50 mg of tramadol hydrochloride as the active ingredient.

It also contains the following inactive ingredients:

  • Microcrystalline cellulose
  • Sodium starch glycollate
  • Colloidal anhydrous silica
  • Magnesium stearate
  • Iron oxide yellow (E172)
  • Indigo carmine aluminium lake (E132)
  • Sodium lauryl sulfate
  • Methyl hydroxybenzoate (E218)
  • Propyl hydroxybenzoate (E216)
  • Gelatin

This medicine contains hydroxybenzoates and sulfites. It is gluten-free, lactose-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

Terry White Chemists Tramadol 50mg capsules (blisters): AUST R 158473.


Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113


Terry White Chemists is a registered trademark of Symbion Pty Ltd.

This leaflet was last updated in:
June 2019.

Published by MIMS August 2019


Brand name

Terry White Chemists Tramadol

Active ingredient

Tramadol hydrochloride




1 Name of Medicine

Tramadol hydrochloride.

6.7 Physicochemical Properties

Tramadol hydrochloride is an odourless, white to off-white crystalline powder that is freely soluble in water and in methanol, very slightly soluble in acetone and has a pKa of 9.41. The water/ n-octanol partition co-efficient is 1.35 at pH 7. It belongs to the synthetic analgesics class and has opioid-like activity.
Chemical Name: (1RS,2RS)-2-(dimethylaminomethyl)- 1-(3-methoxyphenyl)- cyclohexanol hydrochloride.
Chemical Formula: C16H25NO2.HCl.
Molecular Weight: 299.84.

Chemical structure.

CAS number.


2 Qualitative and Quantitative Composition

The capsules contain 50 mg tramadol hydrochloride as the active ingredient.

Excipients with known effect.

Methyl hydroxybenzoate (E218), propyl hydroxybenzoate (E216), gelatin.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hard gelatin capsules having green cap and yellow body filled with a homogeneous white to off-white powder.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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 pre-clinical testing has not completely explained the mode of action, at least two complementary mechanisms appear applicable: binding to mu-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 mu-opioid receptors and higher affinity binding of the principal active metabolite, mono O-desmethyl tramadol, denoted M1, to mu-opioid receptors. In animal models, M1 is up to 6 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 re-uptake 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 post-operative 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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 30 minutes. The absorption half-life (t1/2) is 23 ± 11 minutes.
After oral administration of two 50 mg capsules, the mean absolute bioavailability (fabs) is 68 to 72% and the peak serum level (Cmax) is reached two hours (range: one to three hours) after administration. The mean peak plasma concentration (Cmax) is approximately 280 nanogram/mL after oral administration of two 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 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% those extrapolated from the single dose administration studies with 50 mg capsules. This can be explained by first pass metabolic saturation.


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 concentrations 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-desmethyl tramadol (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 15-19% 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 to 7 hours and the half-life of M1 is 6 to 8 hours. Total clearance is approximately 430 to 610 mL/min.

Pharmacokinetics in patients with hepatic or renal impairment.

Elimination of tramadol and M1 is impaired in patients with hepatic or renal impairment (see Section 4.4 Special Warnings and Precautions for Use). 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 renal impairment including subjects with a considerably decreased creatinine clearance (< 5 mL/min) the mean half-life of tramadol was 11 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%).

5.3 Preclinical Safety Data


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 test 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.


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.

4 Clinical Particulars

4.1 Therapeutic Indications

Relief of moderate to severe pain.

4.3 Contraindications

Tramadol is contraindicated in: 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.

4.4 Special Warnings and Precautions for Use

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 an adverse drug reaction when evaluating altered mental status in these patients if they are receiving tramadol.

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.

Use in renal impairment.

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 (see Section 4.2 Dose and Method of Administration). As tramadol is removed only very slowly by haemodialysis or haemofiltration, post-dialysis administration to maintain analgesia is not usually necessary.

Use in hepatic impairment.

Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. In cirrhotic patients, dosage reduction is recommended (see Section 4.2 Dose and Method of Administration).

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 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 medication that lowers the seizure threshold (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). 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.

Intra-operative use.

In one study using nitrous oxide/ tramadol anaesthetic technique (with only intermittent administration of enflurane 'as required'), tramadol was reported to enhance intra-operative 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 intra-operative recall. Therefore, providing the current practice of administering continuous, potent (volatile or intravenous) anaesthetic agent is followed, tramadol may be used intra-operatively 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 150 mg tramadol per day for up to six months. No clinical studies investigating the safety and efficacy of tramadol beyond six months 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.

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. 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.

Paediatric use.

The use of tramadol is not recommended as safety and efficacy in children have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CNS 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, tranquillisers or sedative hypnotics.
The combination of tramadol with mixed opiate agonists/ antagonists (e.g. buprenorphine, 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 physician 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 Section 4.3 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 hyper-reflexia;
hypertonia and body temperature > 38°C;
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 re-uptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other seizure threshold lowering drugs (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions.

Use with MAO inhibitors.

Tramadol should not be used in patients who are taking MAO inhibitors or who have taken them within the last fourteen days, as tramadol inhibits the uptake of noradrenaline and serotonin (see Section 4.3 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 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 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 of cytochrome P450, 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 pre- or post-operative application of the antiemetic 5-HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No effects on fertility in rats were observed for tramadol at oral dose levels of up to 50 mg/kg/day.
(Category C)
There are no adequate and well controlled studies with tramadol in pregnant women, therefore, tramadol should not be used during pregnancy.
Tramadol has been shown to be embryotoxic and foetotoxic 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 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 (75 mg/kg for rats or 175 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 had decreased weights and pup survival was decreased early in lactation at 80 mg/kg (6 to 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.

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. Chronic use during pregnancy may lead to neonatal withdrawal symptoms. If tramadol were to be used during labour, it may cause respiratory depression in the newborn. 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 is not recommended during breast feeding, 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 microgram of tramadol (0.1% of the maternal dose) and 27 microgram of M1.

4.8 Adverse Effects (Undesirable 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 ≥ 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:

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 free water 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: dyspnoea, 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).


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 tend 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, paraesthesias, tinnitus and unusual CNS symptoms (i.e. confusion, delusions, personalisation, derealisation, paranoia).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.2 Dose and Method of 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.
The recommended dosage of Terry White Chemists Tramadol capsules is as follows:
For the treatment of moderate pain, 50 mg to 100 mg of tramadol administered orally, two or three times daily may be sufficient. An initial dose of 50 mg of tramadol may be sufficient for moderate pain.
For moderate to severe pain, oral doses of 50 mg to 100 mg of tramadol, as needed for pain relief, every four to six hours may be administered. A 100 mg initial dose of tramadol is usually more effective for more severe pain.
The maximum daily dose should not exceed 400 mg per day.


Paediatric use.

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. 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 impairment.

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. Since only 7% of an administered dose is removed by haemodialysis, dialysis patients can receive their regular dose on the day of dialysis.

Hepatic impairment.

In hepatic impairment, the initial oral dose of tramadol is 50 mg. Depending on the severity of impairment and individual clinical response, the recommended dosage interval (4 to 6 hours) may need to be extended, and/or the dose level titrated as required.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

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. 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. If convulsions are observed, diazepam should be given intravenously. 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.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)


6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, sodium starch glycollate, colloidal anhydrous silica, magnesium stearate, iron oxide yellow (E172), indigo carmine aluminium lake (E132), sodium lauryl sulphate, methyl hydroxybenzoate (E218), propyl hydroxybenzoate (E216), gelatin.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

The capsules should be stored below 25°C, and stored in the original package.

6.5 Nature and Contents of Container

Terry White Chemists Tramadol capsules: Packs of 20 capsules. AUST R 158473.
Terry White Chemists is a registered trade mark of Symbion Pty Ltd.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes