Dexketoprofen: A Comprehensive Pharmacological and Clinical Review

1. Introduction to Dexketoprofen

1.1. Overview and Background

Dexketoprofen is a well-established non-steroidal anti-inflammatory drug (NSAID) recognized for its analgesic, anti-inflammatory, and antipyretic properties.[1] It holds a specific place in pharmacology as the S(+)-enantiomer of racemic ketoprofen. This stereoisomer is the pharmacologically active component, responsible for the entirety of the therapeutic effects observed with the parent compound, ketoprofen.[1] The development of dexketoprofen as a single enantiomer represents a "chiral switch" from its racemic predecessor, a strategy aimed at optimizing therapeutic action.[4]

The primary clinical application of dexketoprofen is the symptomatic treatment of mild to moderate acute pain across a variety of conditions.[1] Having first received approval in 1994 [1], dexketoprofen is currently available in numerous countries throughout Europe, Asia, and Latin America, where it serves as a common analgesic option.[1] Its utility is particularly noted in situations requiring prompt pain relief.

1.2. Chemical Properties and Formulation

Chemically, dexketoprofen is identified by the International Union of Pure and Applied Chemistry (IUPAC) name (2S)-2-(3-benzoylphenyl)propanoic acid.[1] Its molecular formula is

C16​H14​O3​, corresponding to a molecular weight of approximately 254.28 g/mol.[1] The Chemical Abstracts Service (CAS) registry number for dexketoprofen is 22161-81-5, and it is cataloged in DrugBank under the ID DB09214.

A crucial aspect of dexketoprofen's clinical utility is its formulation, most commonly as dexketoprofen trometamol. This trometamol salt (also known as tromethamine salt) is a water-soluble form of the drug specifically developed to enhance its physicochemical properties.[4] The improved solubility and absorption characteristics of the trometamol salt lead to a significantly faster onset of action compared to the free acid form of dexketoprofen or racemic ketoprofen.[11] For instance, a 25 mg dose of dexketoprofen (as the active moiety) is equivalent to 36.9 mg of dexketoprofen trometamol.[4] This pharmaceutical refinement is pivotal for its efficacy in acute pain scenarios where rapid relief is paramount.

Table 1: Key Identifiers and Physicochemical Properties of Dexketoprofen

Property	Detail	Source(s)
IUPAC Name	(2S)-2-(3-benzoylphenyl)propanoic acid	1
Common Name	Dexketoprofen	User Query
CAS Number	22161-81-5	1
DrugBank ID	DB09214	User Query
Molecular Formula	C16​H14​O3​	1
Molecular Weight	Approx. 254.28 g/mol	1
Common Salt Form	Dexketoprofen Trometamol	4
Key Property of Salt	Enhanced solubility and rapid absorption	4

The chemical structure and the strategic formulation as a trometamol salt are fundamental to understanding dexketoprofen's pharmacokinetic profile and its advantages in clinical practice, particularly its rapid absorption and onset of analgesic effect.

1.3. Therapeutic Classification

Dexketoprofen is classified as a non-steroidal anti-inflammatory drug (NSAID).[1] Within the broader NSAID category, it belongs to the propionic acid derivatives group, sharing structural and mechanistic similarities with other drugs in this class, such as ibuprofen and naproxen, as well as its parent compound, ketoprofen.[1]

As an NSAID, dexketoprofen exhibits a characteristic triad of pharmacological effects: analgesic (pain-relieving), anti-inflammatory (inflammation-reducing), and antipyretic (fever-reducing) properties.[1] This classification immediately signals a well-understood profile of therapeutic benefits, primarily in managing conditions involving pain and inflammation. Concurrently, this classification also implies a potential for class-specific adverse effects, such as gastrointestinal, renal, and cardiovascular risks, which are inherent to the mechanism of action of NSAIDs and will be discussed in detail in subsequent sections. This early categorization helps to frame expectations regarding both the utility and the safety considerations associated with dexketoprofen.

2. Mechanism of Action and Pharmacology

2.1. Inhibition of Cyclooxygenase (COX) Enzymes

The primary pharmacological action of dexketoprofen is the inhibition of cyclooxygenase (COX) enzymes. These enzymes, existing mainly as COX-1 and COX-2 isoforms, are critical for the conversion of arachidonic acid into prostaglandins.[1] Prostaglandins are lipid autacoids that play a central role as mediators of inflammation, pain perception, and fever.[6] By blocking COX enzymes, dexketoprofen effectively reduces the synthesis of these prostaglandins, thereby alleviating the symptoms associated with inflammatory processes and pain.

The (S)-enantiomer, dexketoprofen, is solely responsible for the COX-1 and COX-2 inhibitory activity previously attributed to racemic ketoprofen.[5] While some investigations have suggested a preferential inhibition of COX-2 over COX-1 by dexketoprofen [11], a more widely accepted characterization describes it as a non-selective or fairly balanced inhibitor of both COX-1 and COX-2 isoforms.[5] This balanced inhibition profile has significant implications. The inhibition of COX-2 is largely responsible for the desired analgesic and anti-inflammatory effects, as COX-2 is typically induced at sites of injury or inflammation. However, the concurrent inhibition of COX-1, which is constitutively expressed and plays a vital role in physiological processes such as maintaining gastric mucosal integrity and normal platelet function [11], means that dexketoprofen carries the risk of side effects commonly associated with traditional NSAIDs, particularly those affecting the gastrointestinal system. This distinguishes dexketoprofen from highly selective COX-2 inhibitors (coxibs), aligning its overall mechanistic profile more closely with conventional NSAIDs.

The inhibition of prostaglandin synthesis not only accounts for dexketoprofen's analgesic and anti-inflammatory actions but also its antipyretic effect. The reduction of fever is specifically attributed to the inhibition of prostaglandin E2 (PGE2) synthesis within the hypothalamus, the brain's thermoregulatory center.[11] Furthermore, the fact that the (S)-enantiomer is the exclusive active moiety for COX inhibition [5] provides the fundamental rationale for the development of dexketoprofen as a chiral switch from racemic ketoprofen. This strategy aims to deliver the therapeutic activity more directly and potentially with an improved therapeutic index by eliminating the inactive or less active (R)-enantiomer.

2.2. Pharmacodynamic Effects

The inhibition of COX enzymes by dexketoprofen translates into several key pharmacodynamic effects:

• Analgesic Effect: Dexketoprofen is effective in providing relief from mild to moderate pain of various origins.[1] Its pain-relieving action is understood to be mediated through both peripheral mechanisms (at the site of injury/inflammation) and central mechanisms within the nervous system.[16]
• Anti-inflammatory Effect: By significantly reducing the production of pro-inflammatory prostaglandins, dexketoprofen diminishes the signs and symptoms of inflammation, such as swelling, redness, and warmth.[1]
• Antipyretic Effect: Dexketoprofen effectively reduces fever. This action is primarily due to the inhibition of prostaglandin E2 synthesis in the hypothalamus, which resets the hypothalamic thermoregulatory set-point closer to normal.[1]

These pharmacodynamic outcomes are the direct result of its interference with the prostaglandin synthesis pathway and form the basis of its clinical applications in managing acute pain and inflammatory conditions.

3. Pharmacokinetics

The pharmacokinetic profile of dexketoprofen, particularly its trometamol salt, is characterized by rapid absorption, limited distribution, extensive metabolism, and relatively quick elimination. These characteristics are crucial for its efficacy and safety in the management of acute pain.

3.1. Absorption and Bioavailability

Dexketoprofen, especially when administered as its trometamol salt, is rapidly absorbed from the gastrointestinal tract following oral administration.[11] The time to reach maximum plasma concentration (Tmax) is notably short, typically ranging from 0.25 to 0.75 hours (15 to 45 minutes).[2] Some sources consistently report a Tmax of around 30 minutes [1], while others indicate a window of 30 to 60 minutes.[11] This rapid attainment of peak plasma levels is a key feature contributing to its fast onset of analgesic action.

The trometamol formulation plays a significant role in this rapid absorption. It enhances the aqueous solubility of dexketoprofen, leading to a faster dissolution rate and subsequently quicker absorption compared to dexketoprofen free acid or racemic ketoprofen.[4] This results in higher peak plasma concentrations (Cmax) and shorter Tmax values, which is directly linked to a more rapid onset of pain relief.[6] This pharmacokinetic advantage conferred by the trometamol salt is a deliberate pharmaceutical strategy to optimize the drug's performance in acute pain situations where immediate relief is highly desirable.

The overall extent of absorption, as measured by the area under the plasma concentration-time curve (AUC) for the (S)-(+)-enantiomer, indicates that oral dexketoprofen (e.g., 25 mg) has a relative bioavailability similar to that of oral racemic ketoprofen (e.g., 50 mg).[17] Studies have shown that the absorption of dexketoprofen from dexketoprofen trometamol capsules is bioequivalent to that of an equivalent dose of the S-enantiomer from racemic ketoprofen.[12]

The presence of food can influence the rate of dexketoprofen absorption. Concomitant administration with food typically delays the absorption rate, leading to an increased Tmax and potentially a reduced Cmax.[7] However, food generally does not significantly affect the total extent of absorption (AUC). Given this food effect, for situations requiring the most rapid onset of action, such as acute pain, administration of dexketoprofen at least 30 minutes before meals is recommended.[6] This presents a practical clinical consideration: while taking dexketoprofen on an empty stomach maximizes the speed of onset, if gastrointestinal discomfort (a common NSAID-related issue) is a concern, administration with food might be preferred, albeit with an acceptance of a potential delay in achieving peak effect.

3.2. Distribution

Once absorbed into the systemic circulation, dexketoprofen exhibits a high degree of binding to plasma proteins, approximately 99%, with albumin being the primary binding protein.[2] This extensive protein binding can have implications for its distribution and potential for drug interactions, particularly with other highly protein-bound medications, as displacement from binding sites can alter the free (pharmacologically active) concentration of either drug.

The apparent volume of distribution (Vd​) of dexketoprofen is reported to be small, generally less than 0.25 L/kg.[14] A small

Vd​ typically suggests that the drug is primarily confined to the bloodstream and extracellular fluid, with limited distribution into deeper tissue compartments. Studies on the disposition of ketoprofen (and by extension, dexketoprofen) in synovial fluid indicate that this process does not appear to be stereoselective.[17] Furthermore, dexketoprofen trometamol is not known to accumulate in adipose tissues.[17]

3.3. Metabolism and Excretion

Dexketoprofen undergoes extensive biotransformation in the liver prior to its elimination. The primary metabolic pathway is glucuronidation, where dexketoprofen is conjugated with glucuronic acid to form an acyl-glucuronide metabolite.[1] This process converts the lipophilic drug into a more water-soluble compound, facilitating its excretion.

In addition to glucuronidation, dexketoprofen is also metabolized to a lesser extent by hepatic cytochrome P450 (CYP) enzymes, specifically CYP2C8 and CYP2C9.[1] This oxidative pathway leads to the formation of hydroxylated metabolites. However, in humans, hydroxylation is considered a minor metabolic route for dexketoprofen.[1] The metabolites formed, primarily the glucuronide conjugate, are largely pharmacologically inactive.[17]

Elimination of dexketoprofen and its metabolites occurs predominantly via the kidneys. Approximately 70-80% of an administered dose is recovered in the urine within the first 12 hours post-ingestion, mostly in the form of the acyl-glucuronide conjugate.[2] A critical pharmacokinetic characteristic of dexketoprofen is the absence of significant chiral inversion in humans. Following administration of the (S)-(+)-enantiomer (dexketoprofen), no (R)-(-)-ketoprofen is detected in the urine.[2] This lack of inversion is a significant advantage, as it ensures that the administered active form remains as such, leading to predictable pharmacodynamics and avoiding potential complexities or contributions to side effects from the (R)-enantiomer or its metabolic fate. This stereochemical stability reinforces the rationale behind the chiral switch from racemic ketoprofen, as it ensures that the patient is exposed only to the therapeutically active isomer.

While glucuronidation is the major metabolic pathway, the involvement of CYP2C8 and CYP2C9, even if minor, raises the possibility of drug interactions with potent inhibitors or inducers of these specific enzymes. This should be considered when dexketoprofen is co-administered with other medications metabolized through these pathways.

3.4. Key Pharmacokinetic Parameters and Influencing Factors

The biological half-life (t1/2​) of dexketoprofen is relatively short, consistently reported as approximately 1.65 hours.[1] Some sources may cite a plasma half-life in the range of 4-6 hours [14], but the 1.65-hour value appears more specific to the elimination phase of dexketoprofen itself in detailed pharmacokinetic studies. This short half-life, combined with its rapid absorption, contributes to its suitability for acute pain management, allowing for flexible dosing intervals (e.g., every 4-8 hours) without undue risk of accumulation.

Indeed, studies have demonstrated that no significant drug accumulation occurs with repeated oral doses of dexketoprofen, such as 25 mg administered two or three times daily.[2] The pharmacokinetic parameters observed after multiple doses are similar to those seen after a single dose.

Pharmacokinetic parameters can be influenced by patient-specific factors. Dosage adjustments are necessary for certain special populations, including elderly patients and individuals with mild to moderate hepatic or renal impairment, to account for potential alterations in drug clearance and to minimize the risk of adverse effects.[7] These adjustments are discussed further in Section 6.

Table 2: Summary of Key Pharmacokinetic Parameters of Dexketoprofen (Trometamol Salt)

Parameter	Value / Description	Key Influencing Factors	Source(s)
Tmax (Oral)	0.25 - 0.75 hours (15-45 min); approx. 30 min	Trometamol salt (faster), Food (slower rate)	1
Cmax (Oral, 25 mg)	Approx. 3.7 ± 0.72 mg/L	Trometamol salt (higher)	1
Bioavailability	Similar to racemic ketoprofen (for S-enantiomer)	Trometamol salt (rapid absorption)	12
Half-life (t1/2​)	Approx. 1.65 hours (elimination)	-	1
Volume of Distribution (Vd​)	<0.25 L/kg	-	14
Protein Binding	Approx. 99% (primarily albumin)	-	2
Primary Metabolism Route	Hepatic glucuronidation; minor CYP2C8/CYP2C9 oxidation	-	1
Primary Excretion Route	Renal (approx. 70-80% in urine as metabolites)	-	2
Chiral Inversion	Absent in humans	-	2
Drug Accumulation	Not significant with repeated doses	-	2

4. Clinical Efficacy

Dexketoprofen has demonstrated efficacy in a range of acute pain conditions, supported by numerous clinical trials and post-marketing experience. Its rapid onset of action and potent analgesic properties make it a valuable therapeutic option.

4.1. Approved Indications and Therapeutic Uses

Dexketoprofen is primarily indicated for the symptomatic treatment of mild to moderate acute pain.[1] Its versatility is reflected in the breadth of specific conditions for which it is approved and used:

• Musculoskeletal Pain: This includes conditions such as muscular sprains and strains, acute low back pain, and the pain associated with osteoarthritis flare-ups.[4]
• Dysmenorrhea: Dexketoprofen is effective for relieving primary menstrual pain.[1]
• Dental Pain: It is widely used for toothache and for managing pain following dental procedures, such as third molar extractions.[1]
• Postoperative Pain: Dexketoprofen is employed for the management of pain following various surgical interventions.[2]
• Renal Colic Pain: It has also found application in alleviating the acute, severe pain associated with renal colic.[2]
• Migraine: Dexketoprofen is used in the treatment of acute migraine attacks.[8]

The consistent efficacy of dexketoprofen across these diverse acute pain states, which often involve both nociceptive and inflammatory components, aligns with its mechanism of action as an inhibitor of prostaglandin synthesis. Its broad utility underscores its role as a first-line or adjunctive analgesic when rapid and effective pain relief is beneficial.

4.2. Evidence from Clinical Trials in Acute Pain Conditions

Clinical studies have evaluated dexketoprofen's efficacy across its indicated uses:

• 4.2.1. Postoperative Pain: In the context of postoperative dental pain, specifically after third molar extraction, oral dexketoprofen at doses of 25 mg and 50 mg demonstrated an onset of analgesic effect within 30 minutes, with pain relief persisting for up to 6 hours.13 A fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg was found to be superior in efficacy to either component administered alone (even tramadol at a higher dose of 100 mg) for moderate-to-severe acute pain following total hip arthroplasty.22 Furthermore, in patients undergoing laparoscopic cholecystectomy, preemptive intravenous administration of dexketoprofen 50 mg showed comparable efficacy to preemptive intravenous ibuprofen 800 mg in terms of postoperative pain scores and opioid consumption, with both active treatments being superior to placebo.25
• 4.2.2. Musculoskeletal Pain: For acute non-traumatic musculoskeletal pain presenting in the emergency department, intravenous dexketoprofen 50 mg provided superior analgesia compared to intravenous paracetamol 1000 mg, as assessed by Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS) scores at 15, 30, and 60 minutes post-administration.27 A post-marketing surveillance study conducted in the Philippines involving adults with osteoarthritis and low back pain also reported statistically significant improvements in pain scores following treatment with dexketoprofen.21
• 4.2.3. Dental Pain: Clinical comparisons have established that dexketoprofen trometamol 25 mg is at least as effective as racemic ketoprofen 50 mg in managing postsurgical dental pain, with the added advantage of a more rapid onset of action for dexketoprofen.5
• 4.2.4. Dysmenorrhea: Dexketoprofen 25 mg has been shown to be as effective as ketoprofen 50 mg in alleviating the pain associated with menstruation.5 When compared to paracetamol for dysmenorrhea, some studies suggest dexketoprofen offers more effective pain relief, although one comparative study, while noting higher VAS scores after dexketoprofen, did not find a statistically significant difference between the two treatments.2
• 4.2.5. Migraine: A clinical trial (NCT04252521) was designed to compare the efficacy of intravenous metoclopramide versus dexketoprofen trometamol, and their combination, in the acute treatment of migraine.23 Evidence also suggests that the combination of metoclopramide and dexketoprofen can yield better outcomes for migraine sufferers than either drug used as monotherapy.2

4.3. Comparative Efficacy (vs. Placebo, Ketoprofen, other NSAIDs, Paracetamol)

Comparisons with other analgesics and placebo provide a clearer perspective on dexketoprofen's relative efficacy:

• Versus Placebo: In studies of postoperative dental pain, dexketoprofen at doses of 12.5 mg, 25 mg, and 50 mg was consistently and significantly more effective than placebo in providing pain relief.[13]
• Versus Ketoprofen: A key finding is that dexketoprofen 25 mg demonstrates efficacy at least comparable to that of racemic ketoprofen 50 mg in indications such as postoperative dental pain and dysmenorrhea.[5] Often, dexketoprofen trometamol exhibits a faster onset of action.[5] This supports the pharmacological principle that by isolating the active S(+)-enantiomer, equivalent therapeutic effects can be achieved with half the dose of the racemate.
• Versus Paracetamol: Dexketoprofen generally shows superior analgesic efficacy compared to paracetamol in various acute pain models, including non-traumatic musculoskeletal pain and general pain relief assessed within 30-60 minutes of administration.[2] For primary dysmenorrhea, the comparative results are somewhat mixed; while some data point to dexketoprofen's superiority, other studies have not found a statistically significant difference.[2]
• Versus Ibuprofen: In the setting of preemptive analgesia for laparoscopic cholecystectomy, intravenous dexketoprofen 50 mg and intravenous ibuprofen 800 mg demonstrated similar efficacy in terms of postoperative pain control and opioid requirements.[25]
• Number Needed to Treat (NNT): The NNT is a clinically relevant measure of analgesic efficacy, representing the number of patients who need to be treated with the active drug for one additional patient to achieve a specified level of pain relief compared to placebo. For dexketoprofen, in achieving at least 50% pain relief over 4–6 hours compared to placebo, an NNT of 2.6 has been reported.[31] This NNT is comparable to that of other commonly used NSAIDs like ibuprofen 200–600 mg (NNTs 2.2–2.8) and diclofenac 50 mg (NNT 2.1), and more favorable than that of paracetamol 1000 mg (NNT 3.7).[31]

A Cochrane review focusing on acute postoperative pain reported an NNT of 4.1 (95% CI 3.3 to 5.2) for dexketoprofen 20/25 mg versus placebo for at least 50% pain relief over six hours.29 The same review reported an NNT of 2.9 for ketoprofen 50 mg. Both drugs showed better efficacy in dental surgery studies compared to other types of surgery.29 The slight discrepancy in NNT values (2.6 vs. 4.1) between these sources may be attributable to differences in the types of pain studies included in the meta-analyses or variations in methodological approaches. Nevertheless, both NNT values fall within a range indicative of effective analgesia. The context, such as the specific type of pain being treated, is important when interpreting NNTs, as efficacy can vary.

Table 3: Overview of Clinical Efficacy of Dexketoprofen in Key Acute Pain Indications

Indication	Comparator(s)	Key Efficacy Outcome(s)	NNT (vs. Placebo, for ≥50% pain relief)	Source(s)
Postoperative Dental Pain	Placebo, Ketoprofen 50 mg	Faster onset (30 min), sustained relief (6 hrs); Dex 25/50mg ≥ Keto 50mg	2.7 (dental studies)	5
Postoperative Pain (General)	Placebo, Ibuprofen, Tramadol	Dex/Tramadol combo superior; Preemptive Dex similar to Ibuprofen	4.1 (overall surgery)	22
Musculoskeletal Pain	Paracetamol	Dex IV superior to Paracetamol IV for acute pain; Effective for LBP, OA	2.6 (general acute pain)	21
Dysmenorrhea	Ketoprofen 50 mg, Paracetamol	Dex 25mg as effective as Keto 50mg; Generally superior or similar to Paracetamol	Not specified in snippets	2
Migraine	Metoclopramide	Dex + Metoclopramide combo may be superior to monotherapy	Not specified in snippets	2

4.4. Onset and Duration of Action

A hallmark of dexketoprofen, particularly its trometamol salt, is its rapid onset of action. Analgesic effects are typically observed within 30 minutes of oral administration.[2] This is notably faster than what is generally observed with racemic ketoprofen [13] and is a direct consequence of the enhanced absorption characteristics of the trometamol formulation. This rapid onset is a significant clinical advantage in acute pain settings where patients prioritize immediate relief.

The duration of the analgesic effect of dexketoprofen is approximately 4 to 6 hours.[13] This duration supports dosing regimens of every 4 to 8 hours for sustained pain control. It is important to reiterate that dexketoprofen is intended for short-term use, with treatment typically limited to the symptomatic period.[7]

5. Safety and Tolerability Profile

The safety profile of dexketoprofen is consistent with that of other non-steroidal anti-inflammatory drugs (NSAIDs). While generally well-tolerated in short-term use for acute pain, it is associated with potential adverse effects, primarily affecting the gastrointestinal system, and carries warnings common to the NSAID class.

5.1. Common and Serious Adverse Effects

Adverse effects are typically categorized by frequency. The Summary of Product Characteristics (SmPC) provides a detailed account.[7]

• Common (affecting ≥1/100 to <1/10 people):
• Gastrointestinal disorders: Nausea, vomiting, abdominal pain, dyspepsia (indigestion), heartburn, and diarrhea are the most frequently reported.[3] Other common GI effects include gastritis, constipation, dry mouth, and flatulence.[7]
• Nervous system disorders: Headache, dizziness, and somnolence (drowsiness) are common.[3] Insomnia and anxiety may also occur.[7]
• General disorders and administration site conditions: Fatigue, pain (other than that being treated), asthenia (weakness), rigors, and malaise can occur.[7] For parenteral formulations, injection site reactions such as pain, inflammation, hemorrhage, or bruising are common.[35]
• Skin and subcutaneous tissue disorders: Skin rash is a common adverse effect.[7]
• Vascular disorders: Flushing may be experienced.[7]
• Uncommon (affecting ≥1/1,000 to <1/100), Rare (affecting ≥1/10,000 to <1/1,000), and Very Rare (<1/10,000) (Serious) Adverse Effects:
• Gastrointestinal disorders: More serious events include peptic ulcer, gastrointestinal hemorrhage, and gastrointestinal perforation, which can be life-threatening. Pancreatitis is a rare complication.[3]
• Hepatobiliary disorders: Hepatocellular injury and abnormal liver function tests are rare.[7]
• Renal and urinary disorders: Acute renal failure, polyuria, nephritis, and nephrotic syndrome can occur, particularly in susceptible individuals.[7]
• Blood and lymphatic system disorders: Neutropenia and thrombocytopenia are very rare.[7]
• Immune system disorders: Hypersensitivity reactions can range from skin rashes and urticaria to more severe manifestations such as laryngeal edema, bronchospasm, dyspnea, angioedema, facial edema, and, very rarely, anaphylactic reaction or shock.[6] Severe cutaneous adverse reactions (SCARs) like Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) are very rare but serious. Photosensitivity reactions and pruritus can also occur.[7]
• Cardiac disorders: Palpitations and tachycardia are uncommon; hypotension may occur very rarely.[7]
• Vascular disorders: Hypertension is rare.[7]
• Respiratory, thoracic and mediastinal disorders: Bradypnea (slow breathing) is rare; bronchospasm and dyspnea are very rare.[7]
• Metabolism and nutrition disorders: Anorexia is rare.[7]
• Musculoskeletal and connective tissue disorders: Back pain has been reported as rare.[7]
• Reproductive system and breast disorders: Menstrual disorders and prostatic disorders are rare.[7]
• Eye disorders: Blurred vision is very rare.[7]
• Ear and labyrinth disorders: Vertigo is uncommon; tinnitus is very rare.[7]

The overall adverse effect profile of dexketoprofen is characteristic of the NSAID class, with gastrointestinal issues being predominant. The potential for serious GI, cardiovascular, and renal events, although less frequent, underscores the importance of careful patient selection, adherence to recommended short-term use, and vigilance for warning signs, especially in at-risk populations.

Table 4: Common and Serious Adverse Effects Associated with Dexketoprofen (Adapted from EMA SmPC [7])

System Organ Class	Common (≥1/100 to <1/10)	Uncommon (≥1/1,000 to <1/100)	Rare (≥1/10,000 to <1/1,000)	Very Rare (<1/10,000)
Blood and lymphatic system disorders				Neutropenia, thrombocytopenia
Immune system disorders			Laryngeal oedema	Anaphylactic reaction (incl. anaphylactic shock)
Metabolism and nutrition disorders			Anorexia
**Psychiatric...source (see section 4.4 of SmPC)	Pancreatitis
Hepatobiliary disorders			Hepatocellular injury
Skin and subcutaneous tissue disorders		Rash	Urticaria, acne, sweating increased	Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioedema, facial oedema, photosensitivity reaction, pruritus
Musculoskeletal and connective tissue disorders			Back pain
Renal and urinary disorders			Acute renal failure, Polyuria	Nephritis or nephrotic syndrome
Reproductive system and breast disorders			Menstrual disorder, prostatic disorder
General disorders and administration site conditions		Fatigue, pain, asthenia, rigors, malaise	Peripheral oedema
Investigations			Liver function test abnormal

5.2. Gastrointestinal Risks

Gastrointestinal (GI) adverse effects are the most commonly encountered with dexketoprofen, a characteristic shared with other NSAIDs.[3] These effects, ranging from dyspepsia and nausea to more severe complications like peptic ulcers, GI bleeding, and perforation, are primarily attributed to the inhibition of COX-1 in the gastric mucosa.[11] COX-1 is responsible for producing prostaglandins that protect the stomach lining. The risk of serious GI events is heightened in patients with a prior history of such conditions, in elderly individuals, and with prolonged NSAID use.[3] Dexketoprofen's indication for short-term use is a key strategy to mitigate these risks.[6]

5.3. Cardiovascular and Renal Safety Considerations

Like other NSAIDs, dexketoprofen use is associated with potential cardiovascular and renal risks. There is an increased risk of arterial thrombotic events, such as myocardial infarction and stroke, particularly with high doses or prolonged exposure, although dexketoprofen is intended for short-term administration.[3] NSAIDs can also cause fluid retention and edema, which may exacerbate hypertension or heart failure.[7]

Renal adverse effects are another concern. Dexketoprofen can lead to impaired renal function and, in some cases, acute renal failure. This risk is more pronounced in patients with pre-existing renal disease, dehydration, the elderly, or those concomitantly using other nephrotoxic drugs or medications that affect renal hemodynamics (e.g., diuretics, ACE inhibitors).[7]

5.4. Contraindications

Due to its mechanism of action and potential for adverse effects, dexketoprofen is contraindicated in several patient populations and clinical situations [7]:

• Known hypersensitivity to dexketoprofen, any of its excipients, or other NSAIDs.
• Patients who have experienced asthma attacks, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema after taking aspirin or other NSAIDs.
• History of photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Active peptic ulcer or gastrointestinal hemorrhage, or any history of recurrent GI bleeding, ulceration, or perforation.
• Chronic dyspepsia.
• Other active bleeding conditions or bleeding disorders, including hemorrhagic diathesis and other coagulation disorders.
• Inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
• Severe heart failure (New York Heart Association [NYHA] Class III-IV).
• Moderate to severe renal impairment (creatinine clearance ≤59 ml/min).
• Severely impaired hepatic function (Child-Pugh score 10-15).
• Severe dehydration (e.g., due to vomiting, diarrhea, or insufficient fluid intake).
• During the third trimester of pregnancy and during the lactation period.

This extensive list of contraindications highlights the necessity for a thorough patient history and clinical assessment before initiating dexketoprofen therapy. Many of these are class-specific contraindications for NSAIDs, reflecting the known risks associated with systemic prostaglandin inhibition.

5.5. Warnings and Precautions

To ensure safe use, several warnings and precautions should be observed:

• The lowest effective dose should be used for the shortest duration necessary to control symptoms.[6]
• Caution is advised in elderly patients, who should typically start therapy at a lower dosage range.[7]
• Patients with a history of allergic disorders or asthma should use dexketoprofen with caution.[6]
• Dexketoprofen may mask the signs and symptoms of infection, potentially delaying diagnosis and appropriate treatment.
• There is a risk of bronchospasm in susceptible individuals.
• Although intended for short-term use, if prolonged administration were to occur, monitoring of renal, hepatic, and hematopoietic function would be advisable.
• Dexketoprofen may cause dizziness or drowsiness in some individuals. Patients should be advised to exercise caution when driving or operating heavy machinery until they are aware of how the medication affects them.[16]

5.6. Drug Interactions

Dexketoprofen has the potential to interact with several other medications, which can alter its efficacy or increase the risk of adverse effects. Clinically significant interactions include [18]:

• Other NSAIDs (including high-dose aspirin): Concomitant use significantly increases the risk of gastrointestinal ulceration and bleeding due to synergistic effects. This combination should generally be avoided.
• Anticoagulants (e.g., warfarin): Dexketoprofen can enhance the effects of anticoagulants, leading to an increased risk of bleeding. Close monitoring of coagulation parameters is essential if co-administration is necessary.
• Antiplatelet agents (e.g., clopidogrel, ticlopidine) and Selective Serotonin Reuptake Inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
• Corticosteroids: Concomitant use increases the risk of gastrointestinal ulceration or bleeding.
• Lithium: NSAIDs can decrease the renal clearance of lithium, leading to elevated plasma lithium levels and potential toxicity. Lithium levels should be carefully monitored.
• Methotrexate: Dexketoprofen can increase the hematological toxicity of methotrexate, particularly when methotrexate is used at high doses (≥ 15 mg/week), by reducing its renal clearance. Caution is advised with lower doses as well.
• Hydantoins (e.g., phenytoin) and Sulphonamides: The toxic effects of these substances may be enhanced.
• Diuretics, ACE inhibitors, Angiotensin II Receptor Antagonists (ARBs): Dexketoprofen may reduce the antihypertensive effect of these drugs. In patients with compromised renal function (e.g., dehydrated patients, elderly), co-administration may lead to a further deterioration of renal function, including possible acute renal failure. Adequate hydration and renal function monitoring are important.
• Pentoxifylline: Increased risk of bleeding.
• Zidovudine: Increased risk of toxicity to red blood cells, potentially leading to severe anemia.
• Sulfonylureas: Dexketoprofen may potentiate the hypoglycemic effect of sulfonylureas. Blood glucose levels should be monitored.
• Ciclosporin and Tacrolimus: Nephrotoxicity of these agents may be increased by NSAIDs through effects on renal prostaglandins. Renal function should be monitored during combined therapy.
• Thrombolytics: Increased risk of hemorrhage.
• Probenecid: Plasma concentrations of dexketoprofen may be increased by probenecid, potentially requiring a dose adjustment of dexketoprofen. This interaction suggests competition for renal tubular secretion.
• Beta-blockers: The antihypertensive effect of beta-blockers may be reduced by NSAID treatment.
• Quinolone antibiotics: Animal data suggest that high doses of quinolones in combination with NSAIDs can increase the risk of convulsions.
• Tenofovir: Concomitant use with NSAIDs may increase plasma urea nitrogen and creatinine; renal function should be monitored.
• Deferasirox: Concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity.
• Pemetrexed: Concomitant use with NSAIDs may decrease pemetrexed elimination; caution is required with high NSAID doses.

Many of these interactions are pharmacodynamic, involving additive effects on physiological systems (e.g., GI tract, coagulation), while others are pharmacokinetic, involving alterations in drug absorption, distribution, metabolism, or excretion. Careful review of concomitant medications is crucial before initiating dexketoprofen.

Table 5: Clinically Significant Drug Interactions with Dexketoprofen

Interacting Drug/Class	Potential Consequence	Management Recommendation/Clinical Implication	Source(s)
Other NSAIDs (incl. Aspirin)	Increased risk of GI ulceration/bleeding	Avoid concomitant use	18
Anticoagulants (e.g., Warfarin)	Enhanced anticoagulant effect, increased bleeding risk	Monitor coagulation parameters closely; use with caution	18
Antiplatelet agents (e.g., Clopidogrel)	Increased risk of GI bleeding	Use with caution	33
Corticosteroids	Increased risk of GI ulceration/bleeding	Use with caution	33
Lithium	Increased plasma lithium levels, potential toxicity	Monitor lithium levels; adjust lithium dose if needed	33
Methotrexate (especially high doses)	Increased hematological toxicity of methotrexate	Avoid with high-dose methotrexate; use with caution and monitor with low-dose methotrexate	33
Diuretics, ACE Inhibitors, ARBs	Reduced antihypertensive effect; risk of acute renal failure in susceptible patients	Ensure hydration; monitor renal function and blood pressure	18
Sulfonylureas	Increased hypoglycemic effect	Monitor blood glucose levels	18
Ciclosporin, Tacrolimus	Increased nephrotoxicity	Monitor renal function	18
Probenecid	Increased plasma concentrations of dexketoprofen	Potential need for dexketoprofen dose reduction	18

6. Dosage and Administration

Appropriate dosage and administration of dexketoprofen are essential for maximizing efficacy while minimizing the risk of adverse events. Recommendations vary based on the patient population and the formulation used.

6.1. Recommended Dosing Regimens

• Adults (Oral): The generally recommended oral dosage for adults is 12.5 mg every 4 to 6 hours, or 25 mg every 8 hours.[4] The choice between these regimens depends on the nature and severity of the pain. The total daily oral dose should not exceed 75 mg.[4]
• Adults (Parenteral - IV/IM): For moderate to severe acute pain where parenteral administration is appropriate, the recommended dose is 50 mg administered every 8 to 12 hours. If necessary, the dose may be repeated after 6 hours. The maximum total daily parenteral dose is 150 mg. Parenteral therapy should be transitioned to oral treatment as soon as clinically feasible.[18]
• Duration of Use: Dexketoprofen is intended for short-term use only. Treatment should be limited to the symptomatic period.[6]

6.2. Special Populations

Dosage adjustments or specific precautions are necessary for certain patient groups due to potential alterations in pharmacokinetics or increased susceptibility to adverse effects:

• Elderly Patients: It is recommended that elderly patients initiate therapy at the lower end of the adult dosage range. For oral administration, a total daily dose of 50 mg is often suggested as a starting point. The dosage may be cautiously increased to that recommended for the general adult population only after good general tolerance has been clearly established.[7] This cautious approach is due to the higher likelihood of age-related decline in renal and hepatic function and increased sensitivity to NSAID-related side effects.
• Hepatic Impairment:
• Mild to Moderate (Child-Pugh A/B): Patients should start therapy with reduced doses, typically a total daily oral dose not exceeding 50 mg. Close monitoring of hepatic function is essential.[7]
• Severe (Child-Pugh C, score 10-15): Dexketoprofen is contraindicated and should not be used in patients with severe hepatic impairment.[7]
• Renal Impairment:
• Mildly Impaired (Creatinine Clearance [CrCl] 60 - 89 ml/min): The initial dosage should be reduced, with a total daily oral dose not exceeding 50 mg. Renal function should be monitored.[7]
• Moderate to Severe (CrCl ≤59 ml/min): Dexketoprofen is contraindicated and should not be used in patients with moderate to severe renal impairment.[7]
• Paediatric Population: Dexketoprofen has not been studied in children and adolescents. Therefore, its safety and efficacy in this age group have not been established, and the product should not be used in paediatric patients.[7]

The need for dose reduction in elderly individuals and those with hepatic or renal impairment is a direct consequence of potential alterations in the drug's pharmacokinetic profile (e.g., reduced clearance leading to increased systemic exposure) and a generally heightened susceptibility to the adverse effects of NSAIDs in these populations.

Table 6: Recommended Dosage of Dexketoprofen for Adults and Special Populations

Population	Oral Dosage	Parenteral Dosage (IV/IM)	Maximum Daily Dose (Oral/Parenteral)	Key Considerations	Source(s)
Adults (General)	12.5 mg q4-6h OR 25 mg q8h	50 mg q8-12h (repeat q6h if needed)	75 mg / 150 mg	Short-term use only	4
Elderly	Start with total daily dose of 50 mg; increase cautiously if tolerated	Dose reduction may be needed	50 mg (initial oral)	Increased risk of AEs; monitor tolerance	7
Mild Hepatic Impairment (Child-Pugh A/B)	Start with total daily dose not exceeding 50 mg	Dose reduction may be needed	50 mg (oral)	Monitor closely	7
Severe Hepatic Impairment (Child-Pugh C)	Contraindicated	Contraindicated	-	Do not use	7
Mild Renal Impairment (CrCl 60-89 ml/min)	Start with total daily dose not exceeding 50 mg	Dose reduction may be needed	50 mg (oral)	Monitor renal function	7
Moderate to Severe Renal Impairment (CrCl ≤59 ml/min)	Contraindicated	Contraindicated	-	Do not use	7
Paediatric Population	Not recommended / Not established	Not recommended / Not established	-	Do not use	7

6.3. Method of Administration

• Oral Administration:
• Tablets should be swallowed with an adequate amount of fluid, such as a glass of water.[7]
• For the fastest onset of action in acute pain, it is recommended to administer dexketoprofen at least 30 minutes before meals, as food can delay absorption.[6] However, if gastrointestinal upset (e.g., nausea) occurs, taking the tablets with or after food may help reduce these symptoms, though this may slightly delay the onset of pain relief.[6]
• Dexketoprofen tablets are often scored, allowing them to be divided into equal doses if a 12.5 mg dose is prescribed.[7]
• Parenteral Administration (IV/IM):
• When administered intravenously, dexketoprofen can be given as a slow bolus injection over a period of not less than 15 seconds, or as an infusion diluted in an appropriate volume of solution (e.g., 0.9% NaCl) over 10 to 30 minutes.[18]
• For intramuscular injection, it should be administered as a slow, deep injection into the muscle.[18]

7. Dexketoprofen in Context: The Chiral Switch from Ketoprofen

The development of dexketoprofen is a notable example of a "chiral switch" in pharmaceutical science, where a single, active enantiomer is developed from an existing racemic drug. Understanding this context is key to appreciating dexketoprofen's characteristics.

7.1. Rationale for Chiral Switch

Racemic ketoprofen is a 50:50 mixture of two enantiomers: the S(+)-enantiomer and the R(-)-enantiomer.[5] Extensive research has established that the analgesic and anti-inflammatory activity of ketoprofen resides almost exclusively, if not entirely, within the S(+)-enantiomer, which is dexketoprofen.[2] The R(-)-enantiomer is largely considered to be pharmacologically inactive or significantly less potent with respect to the desired therapeutic effects, and there have been suggestions it might contribute to some side effects, although this is less clearly defined.[3]

The primary rationale for developing dexketoprofen as a single enantiomer (a chiral switch) was to provide a more targeted therapy. The aims included potentially achieving improved efficacy at a lower total drug dose, realizing a faster onset of action, and possibly attaining a better therapeutic index (benefit-to-risk ratio) or enhanced tolerability profile compared to the racemic mixture.[4] By administering only the active S(+)-isomer, the pharmacokinetic profile can be simplified, and the effective therapeutic dosage can theoretically be halved compared to that of the racemate, as the patient is not exposed to the inactive R(-)-enantiomer.[2] This approach is not merely a pharmaceutical repackaging but a scientifically driven effort to optimize therapy by isolating and delivering the pharmacologically active component. This can lead to more predictable dose-response relationships and potentially reduce the metabolic burden associated with an inactive or less active enantiomer.

7.2. Comparative Aspects: Dexketoprofen vs. Racemic Ketoprofen

Direct comparisons between dexketoprofen and racemic ketoprofen highlight several differences and advantages conferred by the chiral switch:

• Efficacy: Dexketoprofen 25 mg is generally considered to be at least as effective as racemic ketoprofen 50 mg in various acute pain models.[5] This supports the principle that the S-enantiomer is responsible for the activity, and half the dose of the racemate is sufficient when the pure active enantiomer is used.
• Onset of Action: Dexketoprofen, particularly in its trometamol salt formulation, typically exhibits a faster onset of analgesic action compared to racemic ketoprofen.[4] This is largely attributed to the more rapid absorption of the trometamol salt.
• Dosage: As a consequence of isolating the active enantiomer, the effective therapeutic dose of dexketoprofen is half that of racemic ketoprofen for achieving comparable analgesic effects.[2]
• Safety and Tolerability:
• Theoretically, by eliminating the R(-)-enantiomer and reducing the overall drug load administered to the patient, dexketoprofen could offer an improved safety profile or be associated with fewer adverse effects.[3]
• A specific advantage has been observed with parenteral administration: intravenous dexketoprofen induces significantly less injection site pain compared to intravenous racemic ketoprofen.[39]
• However, when considering overall systemic adverse events in short-term studies, some clinical comparisons have not demonstrated significant differences in the incidence of common adverse effects between dexketoprofen and racemic ketoprofen when administered at equipotent doses.[13]
• Pharmacokinetics: Dexketoprofen trometamol is characterized by more rapid absorption (shorter Tmax, often higher Cmax) than racemic ketoprofen formulations.[4] Critically, dexketoprofen (the S-form) does not undergo chiral inversion to the R-form in humans.[2] This stereochemical stability ensures predictable exposure to the active enantiomer, unlike racemic mixtures where in vivo inversion of one enantiomer to another can sometimes occur, complicating the pharmacokinetic and pharmacodynamic profile.

While dexketoprofen offers clear pharmacokinetic advantages (faster absorption, absence of inactive enantiomer load, no chiral inversion) and some distinct clinical benefits (faster onset of action, less injection site pain), the extent of improvement in the overall systemic safety profile compared to racemic ketoprofen in short-term use might be modest if the R-enantiomer of ketoprofen is largely inert concerning common NSAID-related side effects. The primary demonstrated benefits appear to lie in optimizing the delivery and action of the therapeutically active moiety. Long-term comparative safety data would be more definitive in elucidating differences in chronic tolerability, but this is less relevant for a drug primarily indicated for acute pain management.

Table 7: Comparative Profile: Dexketoprofen vs. Racemic Ketoprofen

Feature	Dexketoprofen (S(+)-Ketoprofen)	Racemic Ketoprofen ((±)-Ketoprofen)	Source(s)
Active Moiety	Pure S(+)-enantiomer	Mixture of S(+)- and R(-)-enantiomers (50:50)	4
Equivalent Analgesic Dose	25 mg	50 mg	5
Onset of Action (Oral)	Faster (esp. trometamol salt)	Generally slower	4
Absorption Rate (Oral)	More rapid (trometamol salt)	Slower	4
Injection Site Pain (IV)	Significantly less	More frequent and severe	39
Chiral Inversion in Humans	S(+) to R(-) does not occur	R(-) to S(+) inversion may occur to some extent (species-dependent)	2
Key Advantages	Faster onset, half dose for similar efficacy, less injection pain, predictable pharmacokinetics (no inactive isomer/inversion)	Established use, broader availability in some regions (e.g., USA)	2

8. Regulatory Status and Availability

The regulatory approval and market availability of dexketoprofen vary across different geographical regions.

8.1. Approvals in Different Regions

Dexketoprofen is authorized and marketed in numerous countries, particularly in Europe, Asia, and Latin America.[1] It was first approved for medical use in 1994.[1]

The European Medicines Agency (EMA) has granted marketing authorization for dexketoprofen, and its Summary of Product Characteristics (SmPC) serves as a key regulatory document outlining its properties, indications, and conditions of use in European Union member states.[7]

Regarding its status with the United States Food and Drug Administration (FDA), dexketoprofen as a single enantiomer does not appear to be approved for marketing in the USA. In contrast, racemic ketoprofen is an FDA-approved drug (e.g., brand name Nexcede, approved November 25, 2009).[41] While one source [42] mentions "US Approved Rx (1993)" for Dexketoprofen Tromethamine, this information seems to conflict with more definitive data indicating that only the racemate is currently marketed in the US. This distinction in regulatory status between regions is important. The differing availability underscores variations in regional drug approval processes, market dynamics, and pharmaceutical company strategies. The specific reasons for dexketoprofen's non-approval or lack of marketing in the US are not detailed in the provided information but could relate to factors such as the existing market presence of racemic ketoprofen, patent landscapes, or distinct regulatory requirements for chiral switches.

8.2. Common Brand Names

Dexketoprofen is marketed under various brand names globally. Some of the commonly encountered trade names include:

• Keral®: Manufactured by Menarini, this brand is available in countries such as the United Kingdom.[6]
• Enantyum®: Also produced by Menarini, Enantyum® is a brand name used in Latin American countries.[16]
• Arveles®: This brand is available in parts of Europe, Asia, and Latin America.[8]
• Skudexa®: This is a combination product containing dexketoprofen and tramadol.[6]

Other synonyms or local brand names may also exist, such as Desketo.20

9. Conclusion

9.1. Summary of Key Characteristics

Dexketoprofen is the pharmacologically active S(+)-enantiomer of the NSAID ketoprofen, possessing analgesic, anti-inflammatory, and antipyretic properties. Its primary mechanism of action involves the non-selective inhibition of both COX-1 and COX-2 enzymes, thereby reducing prostaglandin synthesis. A key pharmaceutical feature is its formulation as a trometamol salt, which significantly enhances its aqueous solubility and leads to rapid absorption and a fast onset of action, typically within 30 minutes.

Clinically, dexketoprofen has demonstrated efficacy in the short-term symptomatic treatment of various mild to moderate acute pain conditions, including musculoskeletal pain, dental pain, dysmenorrhea, and postoperative pain. Comparative studies and NNT data position it favorably against placebo and other common analgesics like paracetamol, and it offers at least equivalent efficacy to racemic ketoprofen at half the dose, often with a quicker onset.

The safety profile of dexketoprofen is consistent with that of other traditional NSAIDs, with gastrointestinal disturbances being the most common adverse effects. Potential for more serious GI, cardiovascular, and renal events exists, underscoring the importance of its indicated short-term use and adherence to contraindications and warnings, particularly in at-risk populations. The chiral switch from racemic ketoprofen provides advantages such as a more predictable pharmacokinetic profile due to the absence of the R(-)-enantiomer and lack of chiral inversion in humans, alongside the benefit of a faster onset of action. Dexketoprofen represents a refined therapeutic approach within the NSAID class, leveraging stereoselective pharmacology and optimized formulation (trometamol salt) to enhance its utility for acute pain management. While offering rapid and effective analgesia, its use must be balanced against the known class-specific risks inherent to NSAIDs.

9.2. Place in Therapy

Dexketoprofen serves as a valuable therapeutic option for the short-term management of acute mild to moderate pain across a spectrum of etiologies. Its rapid onset of action, a direct result of the trometamol salt formulation, makes it particularly well-suited for clinical situations where prompt pain relief is a priority for the patient.

The decision to use dexketoprofen over other analgesics, such as paracetamol, other NSAIDs (including racemic ketoprofen), or opioid-containing combinations, should be individualized based on a comprehensive assessment of the clinical scenario. This includes the type and severity of pain, patient-specific factors (e.g., co-morbidities, risk factors for NSAID-related complications, previous experiences with analgesics), the desired speed of onset, and regional availability and formulary guidelines. Its established efficacy, coupled with a generally predictable pharmacokinetic and pharmacodynamic profile, positions dexketoprofen as a strong candidate for treating acute pain episodes where NSAID therapy is deemed appropriate and rapid relief is a key therapeutic goal. However, careful consideration of its risk-benefit profile, strict adherence to the recommended short duration of use, and awareness of its contraindications and potential drug interactions are paramount to ensure its safe and effective application in clinical practice. Its differing regulatory status and availability, being common in Europe, Asia, and Latin America but not in the USA (where racemic ketoprofen is available), also influences its place in therapy globally.

Works cited

1. Dexketoprofen | C16H14O3 | CID 667550 - PubChem, accessed June 13, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Dexketoprofen
2. A comparison between dexketoprofen and other analgesics - Directive Publications, accessed June 13, 2025, https://directivepublications.org/jobio/articles/A-comparison-between-dexketoprofen-and-other-analgesics.pdf
3. Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatme, accessed June 13, 2025, https://access.portico.org/Portico/show?content=E-Journal%20Content&cs=ISSN_03790355_1393&auId=ark%3A%2F27927%2Fpjbf78w3c13&auViewType1=PDF
4. Dexketoprofen – Knowledge and References - Taylor & Francis, accessed June 13, 2025, https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Pharmaceutical_medicine/Dexketoprofen/
5. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, accessed June 13, 2025, https://jcdr.net/articles/PDF/338/266_E(s)_F(p)_R(p)_PF_P.pdf
6. Dexketoprofen for pain - Patient.info, accessed June 13, 2025, https://patient.info/medicine/dexketoprofen-for-pain-keral
7. Keral 25 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc) | 159, accessed June 13, 2025, https://www.medicines.org.uk/emc/product/159/smpc
8. What is Arveles used for? - Drugs.com, accessed June 13, 2025, https://www.drugs.com/medical-answers/question--arveles-3567000/
9. dexketoprofen - PharmGKB, accessed June 13, 2025, https://www.pharmgkb.org/chemical/PA166049175
10. Dexketoprofen trometamol | DrugBank Online, accessed June 13, 2025, https://go.drugbank.com/salts/DBSALT002989
11. What is the mechanism of Dexketoprofen Trometamol? - Patsnap Synapse, accessed June 13, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-dexketoprofen-trometamol
12. Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers After Single and Repeated Oral Doses, accessed June 13, 2025, https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W4142947
13. Clinical comparison of dexketoprofen trometamol, ketoprofen, and placebo in postoperative dental pain - Stork, accessed June 13, 2025, https://www.storkapp.me/pubpaper/9882082
14. Dexketoprofen: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed June 13, 2025, https://go.drugbank.com/drugs/DB09214
15. Pharmacology of non-steroidal anti-inflammatory agents | Deranged Physiology, accessed June 13, 2025, https://derangedphysiology.com/main/cicm-primary-exam/nervous-system/Chapter-334/pharmacology-non-steroidal-anti-inflammatory-agents
16. Dexketoprofen - Wikipedia, accessed June 13, 2025, https://en.wikipedia.org/wiki/Dexketoprofen
17. Clinical Pharmacokinetics of Dexketoprofen | Request PDF - ResearchGate, accessed June 13, 2025, https://www.researchgate.net/publication/11970456_Clinical_Pharmacokinetics_of_Dexketoprofen
18. Dexketoprofen : Indications, Uses, Dosage, Drugs Interactions, Side effects, accessed June 13, 2025, https://medicaldialogues.in/generics/dexketoprofen-2725508
19. Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers After Single and Repeated Oral Doses - PubMed, accessed June 13, 2025, https://pubmed.ncbi.nlm.nih.gov/29023869/
20. Dexketoprofen Trometamol - Drug Targets, Indications, Patents - Patsnap Synapse, accessed June 13, 2025, https://synapse.patsnap.com/drug/dcdac3240d1949e5834fcd8baac4edc7
21. Effectiveness and Safety of Oral Dexketoprofen for Mild to Moderate Pain among Filipino Adults: A Post, accessed June 13, 2025, https://www.omicsonline.org/open-access-pdfs/effectiveness-and-safety-of-oral-dexketoprofen-for-mild-to-moderate-pain-among-filipino-adults-a-postmarketing-surveillance-study-2167-0846-1000319.pdf
22. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty, accessed June 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4718147/
23. Migrainous Headache Completed Phase Trials for Dexketoprofen (DB09214) - DrugBank, accessed June 13, 2025, https://go.drugbank.com/indications/DBCOND0035259/clinical_trials/DB09214?phase=&status=completed
24. Clinical comparison of dexketoprofen trometamol, ketoprofen, and placebo in postoperative dental pain - PubMed, accessed June 13, 2025, https://pubmed.ncbi.nlm.nih.gov/9882082/
25. Efficacy of Preemptive Intravenous Ibuprofen and Dexketoprofen on Postoperative Opioid Consumption in Laparoscopic - medRxiv, accessed June 13, 2025, https://www.medrxiv.org/content/10.1101/2025.01.12.25320436v1.full.pdf
26. Efficacy of Preemptive Intravenous Ibuprofen and Dexketoprofen on Postoperative Opioid Consumption in Laparoscopic Cholecystectomy: Randomized Controlled Study | medRxiv, accessed June 13, 2025, https://www.medrxiv.org/content/10.1101/2025.01.12.25320436v1
27. Intravenous dexketoprofen versus paracetamol in non-traumatic musculoskeletal pain in the emergency department: A randomized clinical trial - PubMed, accessed June 13, 2025, https://pubmed.ncbi.nlm.nih.gov/30744914/
28. Journal of Biomedicines | - Directive Publications, accessed June 13, 2025, https://directivepublications.org/journal-of-biomedicines/a-comparison-between-dexketoprofen-and-other-analgesics
29. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults - PMC, accessed June 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6481461/
30. The comparison of dexketoprofen and other painkilling medications (review from 2018 to 2021) - PubMed, accessed June 13, 2025, https://pubmed.ncbi.nlm.nih.gov/35299123/
31. pmc.ncbi.nlm.nih.gov, accessed June 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2585070/#:~:text=The%20NNT%20for%20dexketoprofen%20compared,NNT%203.7)%20%5B64%5D.%2520%255B64%255D.&sa=D&source=editors&ust=1749809581664837&usg=AOvVaw0NY8vVPqa_RNjF94J7zet8)
32. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults - PubMed, accessed June 13, 2025, https://pubmed.ncbi.nlm.nih.gov/28540716/
33. What is Dexketoprofen Trometamol used for?, accessed June 13, 2025, https://synapse.patsnap.com/article/what-is-dexketoprofen-trometamol-used-for
34. Dexketoprofen: View Uses, Side Effects and Medicines - Truemeds, accessed June 13, 2025, https://www.truemeds.in/drug-salts/dexketoprofen-5172
35. www.mims.com, accessed June 13, 2025, https://www.mims.com/philippines/drug/info/dexketoprofen?mtype=generic#:~:text=Gastrointestinal%20disorders%3A%20Nausea%2C%20abdominal%20pain,inflammation%2C%20haemorrhage%2C%20bruising)..&sa=D&source=editors&ust=1749809581665964&usg=AOvVaw3wLQ-OFktvzjf3kc08OZLZ)
36. Study Evaluating Dexketoprofen Trometamol/Tramadol - ClinConnect, accessed June 13, 2025, https://clinconnect.io/trials/NCT05170841
37. Chiral switch - Wikipedia, accessed June 13, 2025, https://en.wikipedia.org/wiki/Chiral_switch
38. ENANTIOMER (DEXKETOPROFEN) - ARPI, accessed June 13, 2025, https://arpi.unipi.it/retrieve/e0d6c929-defe-fcf8-e053-d805fe0aa794/Mennillo_et_al-2017-Environmental_Toxicology_and_Chemistry.pdf
39. Intravenous dexketoprofen induces less injection pain than racemic ketoprofen | Request PDF - ResearchGate, accessed June 13, 2025, https://www.researchgate.net/publication/277024742_Intravenous_dexketoprofen_induces_less_injection_pain_than_racemic_ketoprofen
40. en.wikipedia.org, accessed June 13, 2025, https://en.wikipedia.org/wiki/Dexketoprofen#:~:text=Dexketoprofen%20is%20a%20nonsteroidal%20anti,as%20Enantyum%2C%20produced%20by%20Menarini.
41. www.accessdata.fda.gov, accessed June 13, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470_nexcede_toc.cfm#:~:text=Approval%20Date%3A%2011%2F25%2F2009
42. DEXKETOPROFEN TROMETHAMINE - Inxight Drugs, accessed June 13, 2025, https://drugs.ncats.io/drug/N674F7L21E