Opioid + NSAID combination Pregnancy: Contraindicated during pregnancy and lactation. Dexketoprofen: inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo-foetal development, with epidemiological concern about increased miscarriage, cardiac malformation and gastroschisis after early-pregnancy use; from the 20th week of pregnancy onward use may cause oligohydramnios from foetal renal dysfunction and ductus arteriosus constriction; in the third trimester all prostaglandin synthesis inhibitors may cause foetal cardiopulmonary toxicity and renal dysfunction, and at the end of pregnancy may prolong bleeding time and inhibit uterine contractions. Tramadol: inadequate evidence in human pregnancy; crosses the placenta; may induce changes in neonatal respiratory rate; chronic use during pregnancy may lead to neonatal withdrawal symptoms.

Tramadol with dexketoprofen

Brand names: Skudexa

A fixed-dose oral combination of the opioid analgesic tramadol with the NSAID dexketoprofen, used for short-term treatment of moderate to severe acute pain. This page covers the combination tablet and its dual analgesic risks.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: One film-coated tablet (corresponding to 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen)

Route: Oral — swallowed with a sufficient amount of fluid (e.g. one glass of water); food delays the absorption rate, so for a faster effect tablets may be taken at least 30 minutes before meals

Frequency: Additional doses can be taken as needed, with a minimum dosing interval of 8 hours

Max: Three film-coated tablets per day (corresponding to 225 mg of tramadol hydrochloride and 75 mg of dexketoprofen); short term use only and treatment strictly limited to the symptomatic period, in any case not more than 5 days

Source is the Skudexa 75 mg/25 mg film-coated tablet SPC (https://www.medicines.org.uk/emc/product/8849/smpc) — both components of the fixed combination are covered. Switching to a single agent analgesia should be considered according to pain intensity and patient response; undesirable effects may be minimised by using the lowest number of doses for the shortest duration necessary. ELDERLY: starting dose one film-coated tablet, additional doses as needed with a minimum interval of 8 hours, not exceeding a total daily dose of 2 film-coated tablets (150 mg tramadol hydrochloride and 50 mg dexketoprofen); may be increased to a maximum of 3 daily tablets only after good general tolerance has been ascertained; limited data in patients over 75 years, so use with caution. HEPATIC IMPAIRMENT: mild to moderate — start at a reduced number of doses (total daily dose 2 film-coated tablets) with close monitoring; must not be used in severe hepatic impairment (Child-Pugh C). Before initiating treatment, agree a treatment strategy including duration, goals and an end-of-treatment plan with the patient; taper the dose gradually on stopping to prevent withdrawal symptoms. PAEDIATRIC (non-numeric, per §4.2): 'The safety and efficacy of Skudexa in children and adolescents have not been established. No data are available. Therefore Skudexa should not be used in children and adolescents.' NOTE ON SOURCES: eMC §4.5 was not captured in the fetched bundle — the interactions listed are drawn from §4.3/§4.4; clinician to check the full §4.5.

Dose adjustments

Renal

The initial total daily dosage should be reduced to 2 film-coated tablets in patients with mildly impaired renal function (creatinine clearance 60-89 ml/min). Must not be used in patients with moderate to severe renal impairment (creatinine clearance <= 59 ml/min) — this is a contraindication.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to dexketoprofen, to any other NSAID, or to any of the excipients; hypersensitivity to tramadol or to any of the excipients
Patients in whom substances with a similar action (e.g. acetylsalicylic acid or other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic oedema
Known photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates
Active peptic ulcer / gastrointestinal haemorrhage, any history of gastrointestinal bleeding, ulceration or perforation (including that related to previous NSAID therapy), chronic dyspepsia
Other active bleedings or bleeding disorders; haemorrhagic diathesis and other coagulation disorders
Crohn's disease or ulcerative colitis
Severe heart failure
Moderate to severe renal impairment (creatinine clearance <= 59 ml/min); severely impaired hepatic function (Child-Pugh C)
Severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake)
Acute intoxication with alcohol, hypnotics, analgesics, opioids or psychotropic medicinal products; patients receiving MAO inhibitors or who have taken them within the last 14 days; epilepsy not adequately controlled by treatment; severe respiratory depression
Pregnancy and lactation

Side effects

Common (Skudexa): nausea, vomiting, diarrhoea, abdominal pain; dizziness, somnolence
Uncommon (Skudexa): headache, constipation, dry mouth, dyspepsia, abdominal discomfort/distension, flatulence, gastritis; insomnia, anxiety, psychotic disorder, amnesia; tachycardia, palpitations, hypotension, orthostatic hypotension, circulatory collapse, flushing, hypertensive crisis; respiratory depression; laryngeal oedema; thrombocytosis, hypokalaemia; hepatic enzyme increased
Rare: dependence, hallucination, confusional state, nightmare, mood altered; epilepsy, tremor, involuntary muscle contractions, paraesthesia, syncope, bradycardia; peptic ulcer, peptic ulcer haemorrhage and perforation; hepatitis, hepatocellular injury; hypersensitivity and anaphylactic reactions including anaphylactic shock
Very rare (single-agent data): neutropenia, thrombocytopenia; bronchospasm, dyspnoea; pancreatitis; tinnitus, blurred vision
Not known: serotonin syndrome; hypoglycaemia; Kounis syndrome; mydriasis; speech disorder; hiccups

Interactions

MAO inhibitors — contraindicated concurrently or within the last 14 days (tramadol component, §4.3)
Other NSAIDs including cyclooxygenase-2 selective inhibitors — concomitant use with dexketoprofen should be avoided (§4.4)
Oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors, and anti-platelet agents such as acetylsalicylic acid — increased risk of gastrointestinal ulceration or bleeding; caution and consideration of gastroprotection (§4.4)
Low dose acetylsalicylic acid and other drugs likely to increase gastrointestinal risk — consider combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) (§4.4)
Diuretic therapy, or states predisposing to hypovolaemia — increased risk of nephrotoxicity with NSAID use; ensure adequate fluid intake (§4.4)

Clinical monograph

How it works

Tramadol is a weak mu-opioid agonist that also inhibits serotonin and noradrenaline reuptake, while dexketoprofen inhibits cyclo-oxygenase to reduce prostaglandin-mediated pain and inflammation; the two provide complementary analgesia.

Prescribing in practice

Combine NSAID and opioid hazards — the dexketoprofen component carries gastrointestinal, renal and cardiovascular risks while tramadol carries respiratory depression, dependence and seizure risk, so use the lowest effective dose for the shortest time.
Tramadol lowers the seizure threshold and can cause serotonin syndrome, so avoid with other serotonergic drugs and in those with epilepsy.
Avoid in active peptic ulceration, significant renal impairment and where NSAIDs or opioids are contraindicated, and limit to short courses.

Monitoring

Monitor pain control, sedation and respiratory status, and watch for gastrointestinal and renal adverse effects during use.

Counselling the patient

Take with or after food and only for short-term pain as directed.
Avoid alcohol and report black stools, indigestion or excessive drowsiness.
Do not take other NSAID or paracetamol-opioid products at the same time without advice.

Evidence & guidelines

The combination is supported by acute-pain trials demonstrating additive analgesia, with safety framed by established NSAID and opioid class data.

Reference: NICE; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways