Tapentadol (Palexia): what it is and how it works

Tapentadol is a strong opioid painkiller, sold in the UK under the brand name Palexia. It is licensed for moderate to severe acute pain in adults and for severe long-term (chronic) pain that can only be managed with an opioid. Tapentadol is a Class A controlled drug, is only available on prescription, and can cause dependence and addiction.

In this guide:

• What tapentadol is
• How tapentadol works
• What tapentadol is used for
• How tapentadol is taken
• Where it fits in UK pain care
• Side effects
• Who should not take it
• Interactions with other medicines and alcohol
• Dependence, addiction and stopping (full guide: tapentadol withdrawal symptoms and stopping safely)
• Legal status, driving and travel

What is tapentadol?

Tapentadol is a prescription painkiller. Its patient leaflet describes it as a pain medicine that “belongs to the class of strong opioids”. That puts it in the same broad group as morphine and oxycodone, rather than with milder painkillers such as paracetamol or ibuprofen. Our guide to tapentadol vs tramadol explains how it differs from tramadol, oxycodone and codeine.

In the UK the best-known brand is Palexia, made by Grünenthal. You may also see the name tapentadol hydrochloride (tapentadol HCl). This is the salt form of the medicine used in the tablets. According to the official prescribing information (SmPC) for Palexia 50 mg tablets, each tablet contains 58.24 mg of tapentadol hydrochloride, which is equal to 50 mg of tapentadol. Doses are always written as the amount of tapentadol.

Tapentadol comes in two main tablet types:

• Immediate-release tablets (Palexia film-coated tablets). These start working fairly quickly and are meant for short-term, acute pain.
• Prolonged-release tablets (Palexia SR). These release the medicine slowly over about 12 hours and are meant for severe long-term pain.

If you are living with long-term pain and want to understand the condition and your options first, read our guide to chronic pain.

How does tapentadol work?

Tapentadol has two actions in one molecule. The SmPC describes it as “a strong analgesic with µ-agonistic opioid and additional noradrenaline reuptake inhibition properties”.

In plain terms, that means:

1. It acts on opioid receptors. Tapentadol switches on mu (µ) opioid receptors in the brain and spinal cord. This is the same main target as morphine. It dampens pain signals travelling to the brain.
2. It boosts noradrenaline. Tapentadol also slows the recycling (reuptake) of noradrenaline. Noradrenaline helps the body’s own pain-dampening pathways that run down the spinal cord.

This mix is why tapentadol’s drug class is sometimes described as a “MOR-NRI” (mu-opioid receptor agonist and noradrenaline reuptake inhibitor). For legal and safety purposes, though, it is treated as a strong opioid.

The SmPC also notes that tapentadol works directly, without needing to be changed into an active form in the body first.

Only about 32% of a dose reaches the bloodstream when taken by mouth, because the liver breaks much of it down first. For the immediate-release tablets, the SmPC gives an average half-life of about 4 hours. That is why these tablets are taken several times a day, while the prolonged-release tablets are taken twice a day.

What is tapentadol used for?

Tapentadol is used only for pain that is bad enough to need an opioid. Its UK licences are set out in the SmPCs for each product.

Product	Licensed use in the UK	Who it is for
Palexia film-coated tablets (immediate release)	Moderate to severe acute pain that can be adequately managed only with opioid painkillers	Adults
Palexia SR prolonged-release tablets	Severe chronic pain that can be adequately managed only with opioid painkillers	Adults, and children above 6 years and adolescents

The SmPC for Palexia SR prolonged-release tablets sets out the chronic pain licence. It also contains an important limit: prolonged-release tapentadol should not be used for acute pain after an operation. The SmPC links this to a higher risk of persistent opioid use after surgery and of breathing problems caused by opioids.

Acute pain versus chronic pain

Acute pain is short-term pain, for example after an injury. It is expected to ease as you heal. The SmPC for the immediate-release tablets says they are “intended for acute pain situations” and should not be used longer than necessary.

Chronic pain lasts longer than about three months. Strong opioids are not a first-choice treatment for most long-term pain, as we explain below. When tapentadol is used for chronic pain, it is the prolonged-release form.

What tapentadol is not licensed for

Tapentadol is not licensed in the UK for:

• Mild pain, or pain that milder painkillers can control
• Headaches, period pain or everyday aches
• Anxiety, low mood or sleep problems
• Acute pain after an operation (prolonged-release tablets)
• Children, unless a specialist prescribes a form licensed for their age

Using a strong opioid for anything other than the reason it was prescribed raises the risk of dependence and harm. It is never something to try on your own.

How is tapentadol taken?

Your prescriber decides your dose based on how bad your pain is and which painkillers you have used before. Always take tapentadol exactly as your prescriber tells you. Never take extra doses or share it with anyone.

Immediate-release tablets

• The SmPC says adults usually start with 50 mg every 4 to 6 hours. Higher starting doses may be needed for some people.
• The tablets are taken with enough liquid, with or without food.
• They are meant for short courses only.

Prolonged-release tablets (Palexia SR)

• The SmPC says adults usually start with 50 mg twice a day, about every 12 hours. Your prescriber may adjust this step by step.
• The Palexia SR patient leaflet lists strengths of 50 mg, 100 mg, 150 mg, 200 mg and 250 mg.
• Swallow each tablet whole. Do not split, crush or chew it, because that can release too much medicine at once.
• They can be taken with or without food.

Older adults, and kidney or liver problems

The SmPC says most older people do not need a different dose. People with mild or moderate kidney problems usually do not need a change either. Tapentadol is not recommended for people with severe kidney or liver problems. People with moderate liver problems start on a lower, less frequent dose under close supervision.

Before starting, your prescriber should agree with you how long you will take tapentadol and how treatment will end. This is part of MHRA advice on opioids, covered in more detail below.

Where does tapentadol fit in UK pain care?

Tapentadol is not usually the first painkiller you would be offered. Because it is only for pain that needs an opioid, it may be suggested by a hospital doctor or pain specialist. How it is prescribed after that depends on local NHS arrangements.

Long-term pain: medicines are only part of the picture

For pain that has lasted a long time, the NHS focuses on more than painkillers. Its page on how to get NHS help for your pain says painkillers are generally not seen as the main way to manage long-term pain. It suggests seeing a GP first if you have struggled with pain for more than 12 weeks.

Other NHS options include:

• Specialist pain clinics, which your GP can refer you to
• Pain management programmes, usually run in groups, covering gentle exercise, relaxation and pacing

A pain management programme aims to improve your quality of life, even when it cannot remove the pain. Ask your GP which of these options are available near you.

Side effects of tapentadol

Like all opioids, tapentadol can cause side effects. Most affect the stomach and the nervous system. The lists below come from the official patient leaflets.

For the full list, warning signs and long-term effects, read our guide to tapentadol side effects.

Very common (more than 1 in 10 people)

• Feeling sick (nausea)
• Dizziness and drowsiness
• Headache
• Being sick (vomiting), listed as very common with the immediate-release tablets
• Constipation, listed as very common with the prolonged-release tablets

Common (up to 1 in 10 people)

The Palexia patient leaflet lists common side effects including:

• Decreased appetite, sleep problems and tiredness
• Anxiety, confusion or seeing things that are not there (hallucinations)
• Trembling, flushing and increased sweating
• Diarrhoea, indigestion and dry mouth
• Itching and rash

The prolonged-release leaflet also lists low mood, restlessness, problems concentrating, shortness of breath and swelling caused by fluid build-up.

Serious risks

The SmPC warns about serious risks that every opioid user should know:

• Slowed or shallow breathing (respiratory depression). The risk is higher at higher doses and when combined with other sedating medicines or alcohol.
• Seizures (fits). Tapentadol is not recommended for people with a history of seizures.
• Serotonin syndrome when combined with some antidepressants (see interactions below).
• Tolerance, dependence and addiction, even at prescribed doses.

You can report suspected side effects to the MHRA through the Yellow Card scheme.

Who should not take tapentadol?

According to the SmPC, you must not take tapentadol if you:

• Are allergic to tapentadol or any ingredient in the tablet
• Have significant breathing problems (respiratory depression) and are not in a monitored setting
• Have acute or severe asthma, or a high level of carbon dioxide in the blood
• Have, or might have, a blocked bowel caused by the gut stopping moving (paralytic ileus)
• Have recently taken too much alcohol, sleeping tablets, other strong painkillers or medicines that affect the mind

Extra care is needed if you

• Have a head injury or raised pressure in the skull
• Have had seizures or epilepsy
• Have kidney, liver, gallbladder or pancreas problems
• Have a breathing disorder during sleep, such as sleep apnoea
• Have ever had problems with alcohol, drugs or medicines

Pregnancy and breastfeeding

The SmPC says tapentadol should only be used in pregnancy if the possible benefit outweighs the risk to the baby. It is not recommended during labour or just before birth, and it should not be used while breastfeeding. If you are pregnant, planning a pregnancy or breastfeeding, talk to your prescriber before you start or stop it.

Tapentadol interactions with other medicines and alcohol

Some combinations with tapentadol can be dangerous. Always tell your prescriber and pharmacist about everything you take, including over-the-counter medicines and herbal remedies.

Medicine or substance	Why it matters
Alcohol	Adds to the sedating effect. The SmPC warns this raises the risk of sedation, slowed breathing, coma and death.
Benzodiazepines, sleeping tablets, other opioids, gabapentin or pregabalin	Same added risk of sedation and slowed breathing. Your prescriber will only combine them with great care.
SSRI or SNRI antidepressants, and tricyclic antidepressants	Can cause serotonin syndrome and may increase the risk of seizures.
MAOI antidepressants	Tapentadol should be avoided if you take an MAOI or have taken one in the last 14 days.
Rifampicin, phenobarbital and St John’s wort	Can lower the level of tapentadol in the blood, so it may work less well.
Ketoconazole and fluconazole	Can raise the level of tapentadol in the blood.

If you take an antidepressant, ask your prescriber or pharmacist which warning signs of serotonin syndrome to look out for.

If you also take a sleeping tablet, check with your prescriber. Our guide to zopiclone explains why combining a sleeping tablet with an opioid needs care.

Dependence, addiction and stopping tapentadol

All opioids can cause dependence and addiction, and tapentadol is no exception. The patient leaflet says plainly that it “can cause dependence and/or addiction”.

What the MHRA says

In September 2020, the UK medicines regulator issued a Drug Safety Update on opioid dependence and addiction. It followed a review by an expert working group of the Commission on Human Medicines, set up in 2019. Tapentadol was among the medicines covered.

Key points from the update include:

• Using opioids for longer than 3 months for pain not caused by cancer carries a higher risk of dependence and addiction.
• Dependence can happen even at prescribed doses.
• Your prescriber should agree a treatment plan with you, including a plan for ending treatment, before you start.
• The Commission recommended that all UK opioid packs carry the warnings “Can cause addiction” and “Contains opioid”.

Signs you may be becoming addicted

The MHRA’s guidance on opioid medicines and the risk of addiction lists warning signs. These include:

• Craving the medicine, or thinking about it a lot
• Needing more than you were prescribed to get the same pain relief
• Using other opioids to top up
• Taking it for reasons other than pain
• Feeling unwell when you stop it suddenly

If any of these sound familiar, talk to your GP or pharmacist. You will not be judged, and getting help early makes a difference.

Stopping tapentadol safely

Do not stop taking tapentadol suddenly unless your doctor tells you to. Stopping abruptly after regular use can cause withdrawal symptoms. Your prescriber will plan any reduction with you, usually lowering the dose gradually. The speed depends on your dose and how long you have taken it, so only your prescriber can set it. Our guide to tapentadol withdrawal symptoms covers this in more detail.

Is tapentadol a controlled drug in the UK?

Yes. Tapentadol is a Class A controlled drug, the same class as morphine.

In July 2010, the Advisory Council on the Misuse of Drugs recommended controlling tapentadol as Class A. It judged its potential for misuse to be similar to other strong opioids such as morphine. The government then added tapentadol to Class A through the Misuse of Drugs Act 1971 (Amendment) Order 2011, made on 16 March 2011.

Tapentadol is also in Schedule 2 of the Misuse of Drugs Regulations 2001. The 2011 regulations that placed it there explain that the schedule sets rules on supply, possession, record keeping, labelling and destruction.

What this means for you:

• It is only legal to have tapentadol if it has been prescribed for you.
• It is illegal to give or sell your tablets to anyone else.
• Pharmacies must follow stricter rules on record keeping and destruction.
• Return any unused tablets to a pharmacy for safe disposal.

Legal status differs a lot between medicines. Zopiclone, for example, is Class C, while modafinil is a prescription-only medicine.

Tapentadol and driving

The Palexia SmPC says tapentadol may have a major effect on your ability to drive. The patient leaflet adds that it may be an offence to drive if your ability to drive safely is affected.

The UK drug-driving law names morphine and other opioid-based drugs among the prescription medicines it covers. You can drive if your medicine has been prescribed, you follow your healthcare professional’s advice, and it does not make you unfit to drive.

Practical steps:

• Do not drive until you know how tapentadol affects you.
• Do not drive if you feel sleepy, dizzy, confused or slow to react.
• Take extra care when starting tapentadol or changing your dose.

A conviction for drug driving can mean a minimum 1-year driving ban, an unlimited fine, up to 6 months in prison and a criminal record.

Travelling with tapentadol

Because it is a controlled drug, check the rules before you travel. GOV.UK guidance on travelling with medicine containing controlled drugs says you can usually carry up to a 3-month supply of a Schedule 2 medicine without a personal licence. The medicine must have been prescribed for you and carried on your person.

It is recommended that you carry a letter from your prescriber listing your medicines, doses and strengths. Other countries have their own rules, so check them before you travel.

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