Dexketoprofen
Short acting NSAID as the active enantiomer of ketoprofen
Dexketoprofen is the pharmacologically active S enantiomer of the racemic ketoprofen. The Spanish company Laboratorios Menarini launched the compound in 1996 under the brand name Enantyum, and in Germany it is marketed as Sympal, Dexketocam and as generics. As dexketoprofen trometamol it is available in a readily soluble salt form that allows rapid absorption and makes the substance particularly suitable for acute pain states.
By using the pure active enantiomer the dose is roughly halved compared with racemic ketoprofen. The analgesic potency at equivalent dose is comparable to other NSAIDs, but the onset of action is faster, which makes dexketoprofen an attractive alternative in acute musculoskeletal pain, postoperative analgesia and dysmenorrhoea. Treatment is limited to the shortest possible duration because of the typical NSAID side effect profile.
Mechanism of Action
Dexketoprofen non selectively inhibits cyclooxygenase 1 and cyclooxygenase 2. This blocks the conversion of arachidonic acid to prostaglandins, prostacyclin and thromboxanes. Inhibition of COX 2 mediates the analgesic, anti inflammatory and antipyretic effect, while inhibition of COX 1 is responsible for a large part of the gastrointestinal, renal and platelet related side effects.
Because only the active S enantiomer is used, the required dose is roughly halved. The bioavailability of the trometamol salt form is above 90 percent, maximum plasma levels are reached as early as 30 to 60 minutes after oral intake. The half life is 1 to 2 hours and the duration of action is 4 to 6 hours. Parenteral administration allows an even faster onset of action.
Metabolism takes place in the liver by glucuronidation and hydroxylation, and elimination is predominantly renal as the glucuronide. Racemisation into the pharmacologically inactive R enantiomer practically does not occur in the body, which maintains the pharmacological purity of the substance.
Indications
- Acute mild to moderate pain of various origins
- Musculoskeletal pain in low back pain, sciatica, cervicobrachialgia and shoulder arm syndrome
- Dysmenorrhoea during the menstrual period
- Postoperative pain therapy usually as part of a multimodal analgesia
- Dental pain and post traumatic pain of mild to moderate intensity
- Headache and migraine in the acute attack (usually single dose)
The indication is limited to acute therapy; long term treatment with dexketoprofen is not intended. For chronic pain or inflammatory disease other NSAIDs or disease modifying agents are available.
Dosage and Administration
Adults oral: 25 mg (equivalent to 36.9 mg dexketoprofen trometamol) every 8 hours, maximum daily dose 75 mg. Mild cases may be treated with 12.5 mg every 4 to 6 hours. Intake before meals speeds the onset of action, intake with food reduces gastrointestinal side effects.
Parenteral: 50 mg intravenously or intramuscularly every 8 to 12 hours, maximum daily dose 150 mg, maximum treatment duration 2 days, then switch to oral form. Elderly patients: 50 mg daily divided into 2 to 3 single doses, caution because of increased gastrointestinal and renal risk.
Renal impairment: mild to moderate impairment 50 mg per day, severe impairment contraindicated. Hepatic impairment: mild to moderate impairment 50 mg per day, severe impairment contraindicated. Duration: use only short term up to 3 to 5 days, then review of therapy.
Side Effects
Common: nausea, vomiting, abdominal pain, diarrhoea, dyspepsia, dizziness, headache, fatigue, insomnia.
Uncommon: nervousness, tremor, paraesthesia, skin rash, pruritus, palpitations, elevated liver transaminases, tinnitus, urinary disorders.
Rare to very rare: severe gastrointestinal bleeding and ulcers (perforation, haemorrhage), anaphylactic shock, Stevens Johnson syndrome, toxic epidermal necrolysis, bronchospasm in asthmatic patients, acute renal failure, nephrotic syndrome, aseptic meningitis, cardiovascular events (myocardial infarction, stroke).
NSAID class warning: Like all NSAIDs, dexketoprofen increases the cardiovascular risk with longer use at higher doses. Diclofenac and coxibs are considered higher risk, ibuprofen and naproxen more favourable. Dexketoprofen sits in the middle, and the risk grows with duration and dose.
Interactions
- Other NSAIDs, acetylsalicylic acid: additive gastrointestinal bleeding risk, avoid combination
- Anticoagulants (warfarin, phenprocoumon, DOACs), heparins: substantially increased bleeding risk
- SSRIs, SNRIs: increased gastrointestinal bleeding risk
- Corticosteroids: additive ulcer and bleeding risk
- Antihypertensives (ACE inhibitors, ARBs, diuretics, beta blockers): attenuation of the antihypertensive effect
- Lithium, methotrexate, digoxin: elevated plasma levels due to reduced renal elimination
- Ciclosporin, tacrolimus: increased risk of nephrotoxic effects
- Probenecid: reduced renal elimination, elevated plasma levels
- Sulfonylureas, phenytoin: displacement from protein binding, hypoglycaemia or toxicity possible
Special Notes
Contraindications: active peptic ulcer, severe heart failure, ischaemic heart disease, cerebrovascular disease, severe renal or hepatic impairment, third trimester of pregnancy, children under 18 years, bronchial asthma with analgesic intolerance, known hypersensitivity to dexketoprofen, ketoprofen or other NSAIDs.
Gastric protection: in patients with risk factors (age above 60, ulcer history, concomitant corticosteroid or anticoagulant therapy) a proton pump inhibitor is recommended alongside. With short term use and no risk factors gastric protection may be omitted.
Pregnancy: use in the first and second trimester only when clearly indicated, contraindicated in the third trimester because of the risk of premature closure of the ductus arteriosus and of fetal renal damage. Breastfeeding: passes into breast milk, not recommended. Ability to drive: dizziness and visual disturbances possible, individual assessment.
Monitoring: no routine laboratory tests are required for short term use. Patients should be informed about warning signs such as black stools, bloody vomiting, severe abdominal pain, skin changes and unexpected shortness of breath.
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Frequently Asked Questions
Why is dexketoprofen more effective than ketoprofen?
Ketoprofen is a racemate of two enantiomers, only the S enantiomer of which is pharmacologically active. Dexketoprofen contains exclusively the active enantiomer, so the dose can be halved. The analgesic effect per milligram is higher, the onset of action somewhat faster and the side effect profile remains comparable.
How long may I take dexketoprofen?
The drug is designed for short term acute treatment, typically 3 to 5 days. Longer use increases the risk of gastrointestinal, renal and cardiovascular side effects and is not intended outside of clearly defined indications. In case of persistent symptoms the treatment plan should be reassessed by a physician.
Can I combine dexketoprofen with paracetamol?
Yes, combining dexketoprofen with paracetamol is pharmacologically reasonable because the two substances act at different targets. The combination is additive in analgesic effect and is widely used in multimodal pain therapy after surgery. The individual doses must remain within the recommended limits. Two NSAIDs such as dexketoprofen and ibuprofen should not be combined.
May I use dexketoprofen for menstrual pain?
Yes, NSAIDs including dexketoprofen are the first choice in primary dysmenorrhoea. They reduce prostaglandin production in the endometrium and thereby relieve the pain. Taking the drug at the start of menstruation for 1 to 3 days is typical. In case of intolerance it is possible to switch to ibuprofen or naproxen.
Sources
- EMA, European Medicines Agency
- AWMF, S3 guideline on acute perioperative pain therapy
- Gelbe Liste, dexketoprofen active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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