Background: The impact of tramadol in children given acetaminophen-ibuprofen combination therapy is uncertain in acute pediatric pain management. A model describing the interaction between these three drugs would be useful to understand the role of supplemental analgesic therapy.
Methods: Children undergoing tonsillectomy were given oral paracetamol and ibuprofen perioperatively. Blood was taken for paracetamol and ibuprofen drug assay on up to six occasions over 6 h after the initial dose. Tramadol was administered by caregivers for unacceptable postoperative pain. Pain was measured using the Parent's Postoperative Pain Measurement rating two hourly on the first postoperative day. A first-order absorption, one-compartment linear model with first-order elimination was used to describe acetaminophen and ibuprofen disposition. Analgesia was described using an EMAX model extended for three drugs, assuming additive effects. Curve fitting was performed using nonlinear mixed effects models.
Results: Pharmacodynamic parameter estimates, expressed using fractional Hill equation, were maximum effect (EMAX ) 0.65 (95%CI 0.54, 0.74), the concentration of acetaminophen associated with 50% of the maximal drug effect (C50,ACET ) 7.06 (95%CI 7.03, 7.72) mg/L, and the ibuprofen C50 (C50,IBU ) 3.95 (95%CI 2.57, 7.53) mg/L. The Hill coefficient was 1.48 (95%CI 0.92, 2.62) and an interaction term was fixed at zero (additivity). The half-time (t1/2 keo) for equilibration between the plasma and effect site was 0.34 hour (95%CI 0.23, 1.98) for acetaminophen and 1.04 hour (95%CI 0.75, 1.77) for ibuprofen. Tramadol had a C50,TRAM of 0.07 (95%CI 0.048, 1.07) mg/L with a t1/2 keo,TRAM 1.78 hour (95%CI 1.06, 1.96).
Conclusion: Ibuprofen has an EC50 for analgesia in children similar to that of adults (3.95 mg/L; 95%CI 2.57-7.53, vs 5-10 mg/L adults). The maximum effect from combination therapy (ie, 65% reduction in pain score) achieves satisfactory analgesia with commonly used doses but increased dose adds little additional benefit. The addition of tramadol to this analgesic mixture prolongs analgesia duration.
Tramadol is a strong opioid-type painkiller (sometimes called an opiate or narcotic) that's used to relieve moderate to severe pain. It's only available on prescription.
Tramadol comes as tablets, capsules and oral drops, and may be given by injection or drip if you're in hospital.
Invodol, Mabron, Maneo, Marol, Maxitram, Oldaram, Tilodol, Tradorec, Tramquel, Tramulief, Zamadol, Zeridame and Zydol are all brand names for tramadol.
Tramacet contains tramadol in combination with paracetamol.
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What is tramadol used for?
- Short-term relief of moderate to severe pain, for example pain following an operation or injury.
- Relieving chronic moderate to severe pain when weaker painkillers haven't been effective.
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💡Key facts about tramadol
- Tramadol is suitable for adults and children aged 12 years and over.
- Tramadol comes as fast-acting forms that are usually taken three to four times a day, and slow-release forms that are taken once or twice a day.
- Tramadol can be addictive, but addiction is rare when it's taken as directed by a doctor to relieve pain.
- The most common side effects are feeling sick, dizzy or sleepy.
- Don't drink alcohol while taking tramadol.
- It may be an offence to drive while taking tramadol.
- Tramadol is a schedule 3 controlled drug that has the potential to be abused. Keep it safe and never give it to anyone else.
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How does tramadol work?
Strong opioid painkillers like tramadol relieve pain by mimicking the action of naturally occurring pain-reducing chemicals called endorphins. Endorphins are found in the brain and spinal cord and reduce pain by combining with opioid receptors.
Tramadol mimicks the action of our natural endorphins by combining with the same opioid receptors in the brain and spinal cord. This blocks the transmission of pain signals sent by the nerves to the brain and means that even though the cause of the pain may remain, less pain is actually felt.
Tramadol also enhances the activity of certain neurotransmitters in the brain and spinal cord. Neurotransmitters are chemical compounds that act as messengers between the nerve cells. Tramadol enhances the effect of the neurotransmitters serotonin and noradrenaline, and this action also helps relieve pain.
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Is tramadol addictive?
Addiction can be a problem when opioids like tramadol are used recreationally. But if you're taking tramadol to relieve pain, it's highly unlikely that you will get addicted to it in the psychological sense, because you're not taking it to get a 'high'.
If you need to take tramadol for long periods of time your body can become tolerant to it, so it may get less effective and you may then need higher doses to control pain. It is also possible to become dependent on tramadol if you take it for a long time, but this is much less likely than with other opioids. It's not usually a problem when you stop taking it, because withdrawal symptoms can generally be avoided by reducing treatment gradually.
It's important that you don't take a higher dose of tramadol than prescribed by your doctor, or take it for longer than they recommend. When stopping treatment always follow your doctor's instructions.
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Who can and can't take tramadol?
Tramadol is suitable for most adults and children aged 12 years and over.
Tramadol should not be taken by:
- Children under 12 years of age.
- People under the influence of (intoxicated with) alcohol, sleeping tablets, tranquilizers, psychotropic drugs (those affecting mood or emotions) or other opioid painkillers, eg morphine, codeine.
- People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days.
- People with uncontrolled epilepsy.
- People who are allergic to any ingredients of the medicine. If you feel you have experienced an allergic reaction, stop taking the medicine and inform your doctor or pharmacist immediately.
Some people, in particular the elderly, might need a lower tramadol dose or extra monitoring. Make sure your doctor knows if you:
- have kidney or liver problems.
- have a head injury or raised pressure in the brain (intracranial pressure).
- have reduced levels of conciousness.
- have slow, shallow breathing (respiratory depression), or other lung conditions or breathing difficulties, for example asthma.
- have been constipated for more than a week or have inflammatory bowel disease such as ulcerative colitis or Crohn's disease
- have difficulty passing urine, for example due to an enlarged prostate gland
- have an underactive thyroid gland
- have reduced production of natural steroid hormones by the adrenal glands (adrenocortical insufficiency)
- have a condition called myasthenia gravis, in which there is abnormal muscle weakness
- have a history of drug dependence or abuse
- have a history or risk of having convulsions (fits or seizures), eg epilepsy.
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Can I take tramadol while pregnant or breastfeeding?
Tramadol is not normally used during pregnancy because its safety is not established and it could have harmful effects on a developing baby. It could cause withdrawal symptoms in a newborn baby if used during late pregnancy. If you are or think you could be pregnant you should get advice from your doctor before taking tramadol.
Tramadol passes into breast milk in small amounts. If you're breastfeeding you should only take tramadol if you have discussed the risks and benefits with your doctor. If your doctor agrees you can use tramadol while breastfeeding, it's important to monitor the baby and let your doctor know immediately if they become more sleepy than usual, or have any difficulty breastfeeding, breathing difficulties or limpness.
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Dosage: How do I take tramadol and how often?
Your doctor may ask you to take tramadol on a regular basis, or only when needed to relieve pain. Always follow their instructions. These will also be printed on the label that your pharmacist has put on the packet of medicine. If you're unsure about anything ask your pharmacist for advice.
⚠️ Never take tramadol more often or at a higher dose than prescribed by your doctor.
Tramadol comes as fast-acting capsules, soluble tablets, tablets that melt in the mouth (orodispersible tablets) and oral drops. It also comes as slow-release capsules and tablets. The way to take it depends on what form you have been prescribed.
All forms of tramadol can be taken either with or without food.
How do I take fast-acting tramadol?
- Tramadol capsules, soluble tablets, oral drops and orodispersible tablets start to work quickly and their effects wear off after a few hours. Fast-acting forms such as these may be prescribed to take only when needed to relieve pain, or on a regular basis, depending on the cause of your pain.
- The usual dose for a healthy adult is 50mg to 100mg every four to six hours, up to a maximum of 400mg in 24 hours, but always follow the instructions given by your doctor.
- Tramadol soluble tablets should be dissolved in at least 50ml water before taking.
- Tramadol orodispersible tablets should be sucked and then swallowed. Alternatively they can be dispersed in half a glass of water before taking.
How do I take slow-release tramadol?
- Tramadol modified-release capsules and modified-release tablets are designed to release tramadol slowly and continuously over 12 or 24 hours as the medicine passes through the gut. This provides steady blood levels of the medicine over the day and prolonged pain relief. These forms of tramadol are taken on a regular basis to control ongoing pain.
- You may be given a 12-hourly or 24-hourly formulation and it's important to know which you have been prescribed.
- Brands that should be taken twice a day at 12 hour intervals (eg 8am and 8pm) include: Invodol SR, Mabron, Maneo, Marol, Maxitram SR, Oldaram, Tilodol SR, Tramquel SR, Tramulief SR, Zamadol SR, Zeridame SR and Zydol SR.
- Brands that should be taken once a day at the same time each day (every 24 hours) include: Tradorec XL, Zamadol 24hr and Zydol XL.
⚠️ Tramadol modified-release capsules and tablets must be swallowed whole. Do not break, crush or chew them, as this will cause the whole dose to be rapidly absorbed into your body, which could result in an overdose.
- Talk to your doctor if you have trouble swallowing, because some brands of modified-release capsules can be opened so you can swallow just the contents without chewing. Check the leaflet provided with your capsules to see if this is the case.
How long should I take tramadol for?
Keep taking tramadol for as long as your doctor tells you to. If you've been taking it for long periods of time you shouldn't stop taking it suddenly - your dose should be reduced gradually. Always follow your doctor's instructions.
What should I do if I miss a tramadol dose?
This depends on the form of tramadol you're taking and how late you are taking the dose. Read the leaflet provided with your medicine to find out what to do, or call your doctor or pharmacist for advice. Never take a double dose of tramadol to make up for a missed dose.
What if I take too much tramadol?
If you accidentally take more than your prescribed tramadol dose, or if someone has taken a tramadol overdose, you should contact your doctor immediately, or go to the accident and emergency department of your nearest hospital. Take the container with you, even if it's empty.
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Can I drink alcohol while taking tramadol?
No, it's best avoided. Drinking alcohol with tramadol will make you more likely to feel sleepy, dizzy or confused, or get other side effects like blurred vision.
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Can I drive while taking tramadol?
It may be an offence to drive while you are taking tramadol. Do not drive if you think it affects your ability to drive safely, for example if it makes you feel sleepy, dizzy, unable to concentrate or make decisions, or if you have blurred or double vision.
If you are driving dangerously while taking tramadol you will be breaking the law. If you feel you are safe to drive while taking tramadol, it may be sensible to carry your prescription with you in case you are asked to take a saliva test by the police. If you test positive for tramadol there is a medical defence if you are taking it as prescribed, as long as your driving is not impaired.
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What are the side effects of tramadol?
It's hard to predict how likely you are to get side effects from tramadol. It depends on the dose you're taking and any conditions you have that might make you more susceptible to problems. In general, tramadol side effects are more likely with higher doses, but some people are more sensitive to opioids and might get side effects at lower doses - medicines and their possible side effects can affect people in different ways.
The following are some of the side effects that can be associated with tramadol. Ask your doctor or pharmacist for advice if you're troubled by any of these, because there is often a solution.
Very common side effects (affect more than 1 in 10 people)
- Feeling sick.
- Dizziness. Don't drive if affected.
Common side effects (affect between 1 in 10 and 1 in 100 people)
- Feeling sleepy or tired. Don't drive if affected.
- Headache.
- Vomiting.
- Constipation.
- Dry mouth.
- Sweating.
Rare side effects (affect between 1 in 1000 and 1 in 10,000 people)
- Blurred vision. Don't drive if affected.
- Seeing or hearing things that are not really there (hallucinations).
- Confusion.
- Anxiety.
- Sleep disturbances.
- Nightmares.
- Changes in mood.
- Increased blood pressure.
- Pins and needles sensations.
- Tremor or twitching.
- Convulsions.
- Slow, shallow breathing (respiratory depression).
- Slow heart rate (bradycardia).
- Muscle weakness.
- Difficulty passing urine.
If you accidentally take too much tramadol, or if you become very sleepy or have very slow and/or shallow breathing after taking it, you or your carer should contact your doctor immediately or call an ambulance.
If you want any more information about the possible side effects of tramadol, read the leaflet provided with the medicine or talk to your doctor or pharmacist. If you think you have experienced a side effect, did you know you can report this using the yellow card website?
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Can I take other medicines with tramadol?
While you're taking tramadol you should always check with your doctor or pharmacist before taking any non-prescription medicines, to make sure that the combination is safe. However, these are the main things to be aware of:
Painkillers
It's fine to take non-prescription painkillers like paracetamol, ibuprofen or aspirin with tramadol (assuming these are appropriate for you). These are weaker painkillers, but as they work in a different way to tramadol they can attack the pain from a different angle. However, there's no point in taking painkillers that contain codeine, co-codamol or dihydrocodeine with tramadol, since these work in a similar way and can also have similar side effects.
If you find you're still getting pain despite taking tramadol it's best to talk to your doctor. They may be able to increase your tramadol dose or try you on a different painkiller.
Antihistamines
If you need an antihistamine it’s best to go for one that won’t make you sleepy, for example cetirizine or loratadine. Avoid those that can cause drowsiness like chlorphenamine or promethazine, because these will make you more sleepy. They can also increase the risk of getting side effects like a dry mouth, constipation, difficulty passing urine and blurred vision.
Herbal remedies
Avoid taking the herbal remedy St John's wort (Hypericum perforatum), as it can increase the risk of getting side effects from tramadol.
What about prescribed medications?
It's important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start taking tramadol. Some key points are:
You're more likely to feel drowsy or sleepy with tramadol if you take it with other medicines that can cause drowsiness, such as the following:
- antihistamines that cause drowsiness, eg hydroxyzine, promethazine
- antipsychotics, eg haloperidol
- barbiturates, eg phenobarbital, amobarbital
- benzodiazepines, eg diazepam, temazepam
- muscle relaxants, eg baclofen
- other opioids, eg codeine, morphine, fentanyl
- sleeping tablets, eg zopiclone
- tricyclic antidepressants, eg amitriptyline.
There may be an increased risk of a rare but potentially serious side effect known as the 'serotonin syndrome' if you take tramadol with medicines or drugs that increase the levels or activity of serotonin in the nervous system. These include the following:
- dapoxetine for premature ejaculation
- mirtazapine
- selective serotonin reuptake inhibitor antidepressants (SSRIs) such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine or sertraline
- serotonin noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine or duloxetine
- tricyclic antidepressants, eg amitriptyline
- triptans for migraine such as sumatriptan.
If you're taking any of the medicines above you should tell your doctor if you experience symptoms such as confusion, agitation, tremor, muscle twitching, shivering, sweating, racing heartbeat or diarrhoea after taking tramadol as well.
The following medicines may make tramadol less effective at relieving pain so your doctor may prescribe a higher than normal dose if you're taking one of these:
- carbamazepine
- ondansetron.
Tramadol may enhance the anti-blood-clotting effect of warfarin. If you're taking warfarin, your blood clotting time (INR) should be checked when you start and stop treatment with tramadol.
There may be an increased risk of convulsions or seizures if you take tramadol with the following medicines:
- antipsychotic medicines, eg haloperidol
- bupropion
- mefloquine
- SSRI antidepressants, eg fluoxetine
- tricyclic antidepressants, eg amitriptyline.
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Can I travel with tramadol?
Tramadol is a controlled drug. If you're planning to travel abroad with it you should check its legal status in the countries you are travelling through and to.
There are legal limits on how much tramadol you can take abroad with you. If you need to take more than this limit you will have to apply to the Home Office for a licence before you travel. Even if you don't need a licence, if you're taking tramadol abroad it is always a good idea to carry a letter from your doctor that confirms your need for the medicine. You should always carry the medicine in correctly labelled packaging, as dispensed by the pharmacy.