Tramadol

As tramadol acts on the central nervous system, it can cause side effects such as dizziness, sleepiness, nausea and constipation. It also carries recognised risks of dependence, tolerance and addiction. In the UK, tramadol is a prescription-only medicine and a controlled drug.

Treatment should therefore be based on an appropriate clinical assessment. A prescriber will normally consider the type and severity of pain, medical history, other medicines being taken and individual risk factors before deciding whether tramadol is suitable.

Tramadol Pharmacological Profile

Tramadol belongs to the opioid analgesic group of medicines, although its pharmacology is somewhat different from that of many conventional opioids.

Part of its effect comes from activity at μ-opioid receptors within the central nervous system. Tramadol itself has opioid activity, while one of its metabolites, O-desmethyltramadol, also contributes to its pharmacological effect.

There is another part to tramadol's action. It can influence the reuptake of the neurotransmitters noradrenaline and serotonin. These chemical messengers are involved in several functions within the nervous system, including pathways concerned with pain processing.

This mixed mechanism helps explain why tramadol has a different interaction and adverse-effect profile from some other opioid medicines. It also means that medicines affecting serotonin, the central nervous system or tramadol metabolism may be clinically important.

How Does Tramadol Work?

Pain signals travel through the nervous system before being processed by the brain. Tramadol alters aspects of this signalling rather than treating the underlying cause of pain itself.

Its opioid component involves μ-opioid receptors. Activation of these receptors can reduce the transmission and perception of pain signals. The active metabolite O-desmethyltramadol contributes to this opioid activity.

At the same time, tramadol affects noradrenaline and serotonin reuptake. This influences neurotransmitter activity within descending pathways involved in the body's processing of pain.

The effect is not identical in every patient. Differences in the cause of pain, metabolism, other medicines and individual biology can all influence the response. Tramadol should therefore not be expected to provide the same degree of pain relief for everyone.

Absorption, Metabolism and Pharmacokinetics

Tramadol is absorbed after oral administration and then undergoes metabolism, mainly in the liver. The Summary of Product Characteristics for tramadol capsules reports oral absorption above 90%, with mean absolute bioavailability of approximately 70%.

After a single oral dose of an immediate-release capsule or tablet in healthy volunteers, peak plasma concentration has been reported at around 1.6 to 2 hours. Exact pharmacokinetic behaviour can vary according to formulation and the individual taking the medicine.

Two liver enzyme pathways are particularly relevant: CYP2D6 and CYP3A4. CYP2D6 is involved in converting tramadol to O-desmethyltramadol, an active metabolite. Medicines that inhibit or otherwise affect these enzymes may change exposure to tramadol or its metabolites.

Genetic differences in CYP2D6 activity are another reason why people may process tramadol differently. Some individuals produce the active metabolite more quickly or more slowly than others.

The elimination half-life of tramadol is approximately six hours according to product information, although this can be prolonged in some circumstances. Tramadol and its metabolites are largely eliminated through the kidneys.

Kidney or liver impairment may slow elimination. This is one reason why a person's general health and medical history need to be considered before and during treatment.

Immediate-Release and Modified-Release Tramadol

Tramadol is supplied in more than one type of oral formulation. They are designed to release the medicine differently.

These formulations should not be treated as automatically interchangeable.

Modified-release tablets or capsules must be taken according to the instructions for the particular product. They should generally be swallowed as directed rather than crushed or chewed, because damaging the release system can cause the medicine to be released incorrectly.

Patients should follow the formulation and instructions stated on their prescription and medicine packaging.

Clinical Uses of Tramadol

Tramadol is used for moderate to severe pain. Whether it is appropriate depends on the individual situation rather than simply the presence of pain.

For acute pain, a clinician may consider an opioid when the severity of symptoms justifies it and other approaches are not adequate or appropriate. The expected duration of treatment is also relevant.

Longer-lasting pain needs particularly careful assessment. Opioids are not automatically suitable simply because pain has continued for a long period. The underlying cause, previous treatments, functional impact and likely balance between benefit and harm all need consideration.

Regular review is important if tramadol continues to be prescribed.

Tramadol as Part of Pain Management

Pain management is not always based on one medicine. Depending on the cause of pain, treatment can involve other medicines, physical rehabilitation, activity changes or treatment directed at the underlying condition.

A clinician deciding whether tramadol has a place in treatment may consider previous painkillers, other health conditions, current medication, the nature of the pain and how it affects everyday function.

Continued opioid treatment should also be reviewed rather than assumed to remain suitable indefinitely. If useful pain relief or functional improvement is not being achieved, the treatment plan may need reconsideration.

Taking Tramadol Safely

Tramadol should be taken only as prescribed. Patients should not increase the amount or take it more frequently because pain remains troublesome without first discussing this with their prescriber.

Standard and modified-release products behave differently. Instructions supplied with the particular medicine should be followed carefully.

If a dose is forgotten, patients should check the patient information leaflet or speak to a pharmacist or prescriber if unsure what to do. Two doses should not be taken together simply to compensate for a forgotten dose.

Anyone finding that tramadol seems less effective over time should seek medical advice rather than changing their treatment themselves. Reduced effect can have several explanations, including the development of tolerance.

Who May Not Be Suitable for Tramadol?

Tramadol is not suitable for every patient. A prescriber needs to consider individual risks before treatment begins.

Particular care may be required in people with a history of seizures, breathing problems, significant liver or kidney impairment, previous drug or alcohol dependence, head injury or conditions affecting consciousness.

Previous allergy or hypersensitivity to tramadol is also important.

Pregnancy and breastfeeding require specific professional assessment because tramadol can cross the placenta and small quantities of tramadol and its metabolite can pass into breast milk.

Older patients may process medicines differently, particularly when kidney or liver function is reduced or several medicines are being taken.

Patients should give their prescriber an accurate medical and medication history rather than assuming that tramadol is suitable because they have previously taken another painkiller without problems.

Tramadol Drug Interactions

Interactions are particularly important with tramadol because both its opioid activity and its effects on neurotransmitters can be influenced by other substances.

Alcohol and medicines that depress the central nervous system can increase sedation and impairment. Combining opioids with sedating medicines, including benzodiazepines, may increase the risk of severe drowsiness and respiratory depression.

Some antidepressants and other medicines affecting serotonin can increase the possibility of serotonin toxicity. Monoamine oxidase inhibitors (MAOIs) are particularly important and should be discussed with the prescriber.

Tramadol can also increase seizure risk in susceptible people. Combining it with medicines that lower the seizure threshold may add to that risk.

Medicines affecting CYP2D6 or CYP3A4 can alter tramadol metabolism and may change exposure to tramadol or its active metabolite.

Patients should tell their prescriber or pharmacist about prescription medicines, pharmacy medicines, supplements and herbal products they use before starting tramadol.

Side Effects of Tramadol

Like other medicines, tramadol can cause unwanted effects. Not everybody experiences them, and their severity varies.

Common Side Effects

Reported effects include:

• nausea or vomiting
• dizziness
• sleepiness or tiredness
• headache
• constipation
• dry mouth
• sweating

Dizziness or sleepiness can be particularly relevant when driving, working at height or operating machinery.

Persistent or troublesome side effects should be discussed with a healthcare professional.

Serious Adverse Effects

Some reactions need urgent medical assessment.

Serious breathing difficulty, marked reduction in alertness, loss of consciousness, seizures or symptoms of a severe allergic reaction should not be ignored.

Tramadol can also contribute to serotonin syndrome, particularly when combined with other serotonergic medicines.

Severe or unexpected symptoms after taking tramadol should be assessed promptly.

Dependence, Tolerance and Misuse

Tramadol is an opioid and can cause dependence.

Physical dependence means that the body adapts to regular exposure to the medicine. This can lead to withdrawal symptoms if treatment is suddenly stopped after ongoing use.

Tolerance can also develop. This means the same amount of a medicine may have less effect over time. A person who believes tolerance is developing should speak to their prescriber rather than taking additional tramadol.

Addiction is another recognised risk. The likelihood can be influenced by duration of use, individual vulnerability and patterns of medicine use.

Taking more tramadol than prescribed can be dangerous. Combining it with alcohol, sedatives or other central nervous system depressants can further increase harm, including excessive sedation and breathing problems.

These risks are among the reasons opioid treatment should be prescribed and reviewed appropriately.

Withdrawal and Stopping Tramadol

Stopping tramadol suddenly after regular or prolonged use can produce withdrawal symptoms.

These may include restlessness, anxiety, agitation, sweating, shaking, sleep disturbance and other physical or psychological symptoms.

Withdrawal is not necessarily evidence of addiction. Physical dependence can occur during medically supervised opioid treatment as the body becomes accustomed to the medicine.

People who have been using tramadol regularly should speak to their prescriber before stopping. Where a reduction is needed, the approach should be planned for the individual rather than following a general or self-directed withdrawal schedule.

Tramadol and Serotonin Syndrome

Serotonin syndrome is an uncommon but potentially serious reaction caused by excessive serotonergic activity in the nervous system.

Tramadol can affect serotonin signalling. The risk becomes particularly relevant when it is taken with certain antidepressants or other medicines that also increase serotonergic activity.

Possible symptoms can include agitation, confusion, sweating, tremor, muscle changes, increased body temperature and a rapid heartbeat. Symptoms can vary and may progress.

Anyone developing symptoms that could indicate serotonin syndrome should receive prompt medical assessment, particularly when tramadol has been combined with another serotonergic medicine.

Tramadol and Seizure Risk

Seizures have been reported in association with tramadol.

Risk may be greater in people who already have epilepsy or another predisposition to seizures. It may also increase when tramadol is used with certain medicines that reduce the seizure threshold.

This is why a history of seizures and a complete list of current medicines should be discussed with the prescriber before treatment.

A seizure occurring during treatment requires medical assessment.

Driving and Operating Machinery

Tramadol can cause sleepiness, dizziness, blurred vision or reduced concentration. These effects can interfere with the ability to drive or operate machinery safely.

A patient should not drive or use machinery if tramadol is affecting alertness, judgement, coordination or reaction time.

There are also legal requirements concerning driving while impaired by medicines and controlled drugs. Patients should follow current UK guidance and any advice given by their doctor or pharmacist.

Overdose and Emergency Risks

Taking too much tramadol can cause serious poisoning. Risk can become greater when tramadol is combined with alcohol, sedative medicines or other substances that depress the central nervous system.

Possible warning signs of serious toxicity include extreme drowsiness, loss of consciousness, seizures and difficulty breathing.

A suspected overdose should be treated as a medical emergency. Emergency medical assistance should be sought rather than waiting for symptoms to improve.

No additional tramadol should be taken in an attempt to manage uncontrolled pain beyond what has been prescribed.

UK Prescription and Controlled-Drug Status

Tramadol is a prescription-only medicine in the UK. It is also controlled under UK drugs legislation.

Tramadol is classified as a Class C controlled drug and is placed in Schedule 3 of the Misuse of Drugs Regulations 2001. This status places additional legal requirements around prescribing and supply.

Its controlled status reflects the need to balance legitimate medical use with the recognised risks associated with misuse and dependence.

Patients obtaining tramadol through a legitimate UK pharmacy should therefore expect appropriate prescription and clinical requirements to apply. Its supply should not be presented as a way of avoiding medical assessment or prescription controls.

Reviewed by:

Dr. Ashish Dhyani, PhD, MSc, BMLT

Scientific Researcher & Medical Content Specialist