Tapentadol vs tramadol: how they differ, plus oxycodone and codeine

Tapentadol vs tramadol: both are opioid painkillers with an extra action on brain chemicals, but they are not the same medicine. Tramadol needs the liver to turn part of it into an active form and also affects serotonin, while tapentadol works directly and mainly adds a noradrenaline effect. They have different UK licences, different safety warnings and different legal classes.

People often search this comparison after a change in their pain medicine, or when a prescriber suggests one instead of the other. This guide sets out how the two medicines differ, using the official UK product information. It also covers how they compare with oxycodone and codeine. For a full overview of one medicine, read our complete guide to tapentadol.

This guide does not give dose conversions or “strength” ratios. Only your prescriber can decide whether a change is right for you and how to make it safely.

Tapentadol and tramadol at a glance

	Tapentadol	Tramadol
Medicine group	Opioid with noradrenaline reuptake inhibition	Opioid with noradrenaline and serotonin effects
Active form	Works directly, no active metabolite	Partly works through an active metabolite made in the liver
Main liver route	Glucuronidation (cytochrome P450 enzymes play a small part)	CYP2D6 and CYP3A4 enzymes
UK licensed use	Moderate to severe acute pain (IR); severe chronic pain (SR); only when an opioid is needed	Moderate to severe pain
Age (UK licence)	Adults; SR tablets also children over 6 for severe chronic pain	Adults and children aged 12 and over (capsules)
Legal class	Class A, Schedule 2	Class C, Schedule 3

Sources for each row are given in the sections below and in the references list.

How tapentadol and tramadol work

Tapentadol

The Summary of Product Characteristics (SmPC) for Palexia tablets describes tapentadol as a strong painkiller with two actions. It switches on mu-opioid receptors, like other opioids. It also stops nerve cells taking back up noradrenaline, a chemical messenger involved in pain signals.

The SmPC says tapentadol works directly, without a pharmacologically active metabolite. Most of it is broken down by glucuronidation, and none of its breakdown products adds to pain relief.

Tramadol

The SmPC for Zydol 50 mg capsules describes tramadol as a centrally acting opioid. Alongside its opioid effect, it blocks the reuptake of noradrenaline and boosts the release of serotonin.

Part of tramadol’s effect comes from O-desmethyltramadol, a substance the liver makes using the CYP2D6 enzyme. The SmPC says only this metabolite is pharmacologically active. Medicines that block CYP2D6 or CYP3A4 can change the levels of tramadol and its active metabolite.

Why this matters to you

A 2021 review comparing the two medicines (Roulet and colleagues, published in Drugs) explains the practical effect. Because tramadol depends on CYP2D6, people whose CYP2D6 works very fast or very slowly may respond to it differently. Tapentadol’s effect does not rely on that enzyme.

The review also notes that tapentadol’s noradrenaline action is stronger than its serotonin action. In tramadol, one of its two mirror-image forms mainly blocks the reuptake of serotonin.

What each medicine is licensed for in the UK

• Tapentadol immediate-release (IR): moderate to severe acute pain in adults that can be adequately managed only with opioid painkillers, according to the Palexia SmPC.
• Tapentadol prolonged-release (SR): severe chronic pain in adults, and in children over 6 years, that can be adequately managed only with opioids, according to the Palexia SR SmPC.
• Tramadol: moderate to severe pain. The Zydol capsules are for adults and children aged 12 and over. The NHS tramadol guide adds that a doctor may prescribe it for severe pain if weaker painkillers have not helped.

Any use outside these licences is “off-label”. That decision belongs to a specialist prescriber, and this article does not encourage it.

Is tapentadol stronger than tramadol?

There is no simple, safe answer you can act on yourself. The tapentadol SmPC calls it a strong analgesic, and its licence is limited to pain that needs an opioid. The NHS also calls tramadol a strong painkiller.

Legal class is sometimes mistaken for a measure of strength. Tapentadol is Class A and tramadol is Class C, but drug classes reflect the risk of harm and misuse, not how well a medicine eases your pain. How each medicine works for you depends on your pain, your body and your other medicines.

So do not swap one for the other, or change how much you take, without your prescriber. Moving between opioids needs a planned approach, and getting it wrong can cause overdose or withdrawal.

Side effects and safety differences

Both medicines share typical opioid side effects such as feeling sick, constipation, dizziness and drowsiness. Our guide to tapentadol side effects lists them in full. The main differences are below.

Serotonin syndrome

The Zydol SmPC says serotonin syndrome, a potentially life-threatening reaction, has been reported with tramadol combined with other serotonergic medicines, and with tramadol alone. Examples include many antidepressants (SSRIs, SNRIs, tricyclics) and mirtazapine.

Tapentadol is not free of this risk. The MHRA warned in January 2019 that serotonin syndrome has been reported when tapentadol is used with serotonergic antidepressants. The 2021 review concluded tapentadol is likely to cause fewer serotonin-related side effects than tramadol, but more typical opioid effects such as constipation, breathing problems and misuse.

Fits (seizures)

Tramadol must not be used by people whose epilepsy is not controlled by treatment, according to its SmPC. Fits have been reported at recommended doses, mainly with high doses or with other medicines that lower the seizure threshold.

For tapentadol, the MHRA advises prescribing with care in people with a history of seizures or epilepsy. It may also increase seizure risk in people taking other medicines that lower the seizure threshold.

MAOI antidepressants

Tramadol is contraindicated if you take a monoamine oxidase inhibitor (MAOI) or took one in the last 14 days. The Palexia SR SmPC says tapentadol should be avoided in the same situation.

Dependence and addiction

Both are opioids, so both can cause dependence. The MHRA’s September 2020 safety update covers codeine, oxycodone, tapentadol and tramadol. It warns that using opioids for longer than 3 months for non-cancer pain increases the risk of dependence and addiction.

The MHRA asks prescribers to agree a treatment plan, including how treatment will end, before you start. If you want to stop, speak to your prescriber, who will reduce the dose slowly to limit withdrawal effects. Read more about tapentadol dependence and withdrawal.

Tapentadol vs oxycodone (OxyContin)

Oxycodone is sold under brands including OxyContin, OxyNorm, Longtec and Shortec. The NHS oxycodone page says it treats pain after an operation or serious injury and pain from cancer. It is often used for moderate to severe pain when paracetamol and ibuprofen have not worked.

The key difference is the mechanism. Oxycodone is a conventional opioid that works through opioid receptors. Tapentadol adds a noradrenaline action on top of its opioid effect. Both are Class A, Schedule 2 controlled drugs, so the same strict prescription and storage rules apply to both.

Tapentadol vs codeine

Codeine is usually used for milder pain than tapentadol. The SmPC for codeine phosphate 30 mg tablets licenses it for acute moderate pain in people older than 12 that other painkillers such as paracetamol or ibuprofen alone have not relieved. It limits treatment for pain to 3 days.

Codeine has the opposite metabolism to tapentadol. The liver uses CYP2D6 to turn codeine into morphine, its active form. Codeine must not be used by people known to be CYP2D6 “ultra-rapid metabolisers”, by children under 12 or during breastfeeding, because of the risk of opioid toxicity.

Legal status in the UK

All four medicines are controlled under the Misuse of Drugs Act 1971 and the Misuse of Drugs Regulations 2001. The Home Office list of commonly encountered controlled drugs gives these classes and schedules:

Medicine	Class	Schedule
Tapentadol	A	2
Oxycodone	A	2
Codeine	B	2 or 5 (depending on the preparation)
Tramadol	C	3

Our guide to controlled drugs in the UK explains what each class and schedule means for prescriptions, collection and travel.

Driving matters too. The GOV.UK drug-driving page names opioid medicines, including codeine and tramadol, among prescription drugs covered by the law. It is illegal to drive if any medicine affects your ability to drive safely.

Who decides, and can you switch?

The choice depends on the type of pain, how long it is likely to last, your other medicines and your medical history. NICE guidance on neuropathic pain (CG173) recommends amitriptyline, duloxetine, gabapentin or pregabalin first for most nerve pain. It says to consider tramadol only if acute rescue therapy is needed.

The 2021 review concluded that tapentadol is not a first-line opioid and that the overall evidence comparing the two is low quality. That is why switching is a decision for your prescriber or pain team, not something to try yourself. If you have questions about where a medicine came from, our guide on how to check a UK online pharmacy can help.

This article is for information only and does not replace advice from your doctor or pharmacist. Read our medical disclaimer.