Ketoprofen gel for external use 5% 30 g (Vertex)

Ketoprofen gel for external use 5% 30 g (Vertex)

Registration Certificate Holder

VERTEX (Russia)

Dosage form

Medicine - Ketoprofen (Ketoprofen-Vertex)

Description

Gel for external use
1 g
ketoprofen 50 mg

30 g - aluminum tubes (1) - cardboard packs. 50 g - aluminum tubes (1) - cardboard packs.

Indications

Symptomatic treatment of painful and inflammatory processes of various origins, including: rheumatoid arthritis and periarthritis; ankylosing spondylitis (ankylosing spondylitis); psoriatic arthritis; reactive arthritis (Reiter's syndrome); osteoarthritis of various localizations; tendinitis, bursitis; myalgia; neuralgia; radiculitis; injuries of the musculoskeletal system (including sports), bruises of muscles and ligaments, sprains, ruptures of ligaments and muscle tendons.

Contraindications for use

Hypersensitivity to ketoprofen; hypersensitivity to salicylates, tiaprofenic acid or other NSAIDs, fenofibrate, UV blockers, fragrances; violation of the integrity of the skin (eczema, weeping dermatitis, open or infected wound); indications in the anamnesis of attacks of bronchial asthma caused by taking NSAIDs and salicylates; history of photosensitivity reactions; exposure to sunlight, incl. indirect sunlight and UV irradiation in a solarium throughout the entire treatment period and for another 2 weeks after stopping treatment; III trimester of pregnancy; children under 15 years of age.

Carefully

Impaired liver and/or kidney function, erosive and ulcerative lesions of the gastrointestinal tract, blood diseases, bronchial asthma, chronic heart failure.

pharmachologic effect

NSAIDs. It has analgesic, anti-inflammatory and anti-edema effects. Inhibits the activity of COX, which leads to inhibition of prostaglandin synthesis. In addition, ketoprofen inhibits lipoxygenase, bradykinin synthesis, stabilizes lysosomal membranes and prevents the release of enzymes involved in the inflammatory process.

Ketoprofen does not have a negative effect on the condition of articular cartilage.

Drug interactions

Since the concentration of ketoprofen in the blood plasma is extremely low, symptoms of interaction with other drugs (similar symptoms with systemic use) are possible only with frequent and prolonged use.

The simultaneous use of other topical products containing ketoprofen or other NSAIDs is not recommended.

Simultaneous administration of acetylsalicylic acid reduces the degree of binding of ketoprofen to plasma proteins.

Ketoprofen reduces the excretion of methotrexate and increases its toxicity.

Patients taking coumarin-containing anticoagulant drugs are advised to undergo treatment under medical supervision.

Dosage regimen

Apply externally 2-3 times/day.

The duration of treatment without consulting a doctor should not exceed 14 days.

Side effect

Allergic reactions: very rarely - angioedema, anaphylaxis.

From the skin and subcutaneous fat: infrequently - erythema, itching, burning, eczema, mild transient dermatitis; rarely - urticaria, rash, photosensitivity, bullous dermatitis, purpura, erythema multiforme, lichenoid dermatitis, skin necrosis, Stevens-Johnson syndrome; very rarely - a single case of severe contact dermatitis (due to poor hygiene and insolation), a single case of severe generalized photodermatitis, toxic epidermal necrolysis.

From the respiratory system: very rarely - asthmatic attacks (as a variant of an allergic reaction).

From the urinary system: very rarely - deterioration of renal function in patients with chronic renal failure.

special instructions

It is necessary to avoid contact of this product with the eyes, the skin around the eyes, and mucous membranes.

Ketoprofen can be used externally in combination with oral administration. The total daily dose, regardless of the dosage form, should not exceed 200 mg.

To reduce the risk of developing photosensitivity, it is recommended to protect skin areas treated with ketoprofen with clothing from exposure to ultraviolet radiation throughout the entire treatment period and for another 2 weeks after stopping use of the gel.

Do not use as occlusive dressings.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Use is contraindicated in the third trimester of pregnancy. Use in the first and second trimesters is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk for the fetus.

Use during lactation (breastfeeding) is not recommended.

Use for renal impairment

Restrictions in case of impaired renal function - With caution. Use with caution in case of impaired renal function.

Use for liver dysfunction

Restrictions in case of liver dysfunction - With caution. Use with caution in case of liver dysfunction.

Use in elderly patients

Restrictions for elderly patients - Use with caution. Use with caution in elderly patients.

Use in children

Restrictions for children - Contraindicated. Contraindicated: children under 15 years of age.

Terms of sale

The drug is approved for use as a means of OTC.

Ketoprofen in the treatment of acute and chronic pain: review of literature data

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most important class of drugs used to relieve acute and control chronic pain in therapeutic practice. NSAIDs are distinguished by a combination of analgesic, anti-inflammatory and antipyretic effects, which provides them with an advantage over paracetamol and opioids [1–3].

Currently, nineteen different NSAIDs are registered in Russia. These are “international nonproprietary names,” i.e., chemical substances, and there are an order of magnitude more specific commercial drugs. Unfortunately, none of the modern NSAIDs can be considered ideal: if any drug has an advantage in one or another parameter, most likely, it also has serious disadvantages.

The main difference between different representatives of the NSAID group is their safety. Until recently, the main problem with these drugs was the development of complications from the gastrointestinal tract (GIT). All NSAIDs are cyclooxygenase (COX) 2 inhibitors, however, in addition to this action, they can inhibit the structurally similar enzyme COX-1. The work of the latter is necessary to maintain the protective potential of the gastrointestinal mucosa, so its blockade can lead to the development of dangerous gastrointestinal pathology - the so-called. NSAID gastropathy and NSAID enteropathy [4].

Selectivity for COX-2, and therefore the risk of developing gastrointestinal pathology, became the basis for dividing NSAIDs into two groups: “traditional” or non-selective (n-NSAIDs) and selective (s-NSAIDs). s-NSAIDs, so-called. “coxibs” were created in the late 90s of the last century as a safer alternative to “traditional” NSAIDs for the gastrointestinal tract. But, as it turned out, “coxibs” have a serious drawback: selective blockade of COX-2 can disrupt the balance of factors affecting blood clotting - the synthesis of thromboxane A2 and prostacyclin, which determines the prothrombotic effect. In patients with diseases of the cardiovascular system (CVS), this is fraught with an increased risk of thromboembolic complications, such as myocardial infarction (MI) and ischemic stroke [4].

This problem has renewed interest among practitioners in “traditional” NSAIDs, the use of which seemed to be associated with a significantly lower risk of cardiovascular (CV) complications.

But not all n-NSAIDs are safe against cardiovascular disease. Thus, the risk of CV complications when using the most popular representative of the “traditional” NSAIDs in Russia, diclofenac, is very high. This fact is shown by a meta-analysis of 25 population-based studies conducted in 18 independent populations and representing the individual risk of CV complications for different NSAIDs. The outcome measure was the incidence of myocardial infarction, which occurred in ~100,000 patients. Minimal risk of MI was shown for naproxen (odds ratio (OR) 1.06) and celecoxib (OR 1.12); for diclofenac this figure was 1.38 [5].

Another popular n-NSAID, ketoprofen, demonstrates a significantly lower risk of LE complications. This drug appeared in Europe in 1971 and quickly gained a reputation as an effective and reliable analgesic [6]. Over forty years of clinical use, it has not lost its significance. P. Sarzi-Puttini et al. emphasize this fact in a review with a very characteristic title: “Pain and ketoprofen: its role in clinical practice,” which was published in 2010. They point to a huge base of evidence of its effectiveness, a wide range of indications - in fact, all pathological processes accompanied by nociceptive pain, and a good reputation among doctors [7].

Interest in ketoprofen can be assessed by the increase in its prescriptions in European countries. Thus, M. Venegoni et al. showed that, against the backdrop of a small but clear decrease in overall sales of “prescription” NSAIDs in Italy for the period from 2006 to 2009. the popularity of ketoprofen has almost doubled (by 93%). If in 2006 263,897 residents of this country purchased ketoprofen, then in 2009 - already 508,699 [8].

Many experts associate the high analgesic potential of ketoprofen with the characteristics of its molecule. The lipophilicity and relatively small size of ketoprofen determine its ability to easily penetrate into inflamed tissue (for example, into the synovial cavity in arthritis), creating a high concentration [7, 9]. Great importance is attached to the diffusion of ketoprofen through the blood-brain barrier and its effect on the central structures of the pain system. Experimental data confirm the equilibrium concentration of the unbound fraction of ketoprofen in blood plasma and cerebrospinal fluid. Moreover, the central effect of this drug is associated not only with the blockade of COX-2, but also with other mechanisms, in particular, with its effect on the serotonergic antinociceptive system [10].

As noted above, the experience of using ketoprofen includes all diseases and pathological conditions for which the prescription of NSAIDs seems appropriate. Working with ketoprofen is facilitated by the availability of a full range of dosage forms: solution for intravenous (IV) and intramuscular (IM) administration, standard tablets, controlled-release capsules, forms for topical use, rectal suppositories.

Ketoprofen is a very successful remedy for urgent pain relief. In 2009, data from a Cochrane meta-analysis were published evaluating the results of a single dose of ketoprofen at a dose of 25–100 mg for acute postoperative pain. The material was based on data from 14 randomized controlled trials (RCTs) (968 patients treated with ketoprofen, 520 placebo), and the main evaluation criterion was a pain reduction > 50% for a period of 4 to 6 hours. The researchers used the NNT (number need to treat) index, which shows the number of patients who need to be treated to achieve a significant difference from placebo. This index was 2.4–3.3, which shows a fairly high effectiveness of the drug [11].

Data from a large-scale study (n = 338) were recently published, which examined the effect of a single intravenous administration of parecoxib 40 mg and ketoprofen 100 mg for the relief of acute renal colic. Ketoprofen, which acted as a comparison drug, was in no way inferior to the representative of “coxibs”: the reduction in pain (on a visual analogue scale - VAS) 30 minutes after injection was 35.2 ± 26.0 and 33.8 ± 24.6 mm [12 ].

The work of S. Karvonen et al. is an example of the successful use of ketoprofen in surgical practice. Here, ketoprofen at a dose of 300 mg/day was used in 60 patients who had undergone orthopedic surgery. The control group consisted of patients receiving placebo or paracetamol 4 g/day. The criterion for effectiveness, in addition to reducing the severity of pain, was the assessment of the “opioid-sparing” effect, which was determined by comparing the dose of fentanyl required for persistent analgesia. This effect was noted only in the ketoprofen group: the average dose of fentanyl was 22% less than in the placebo group and 28% less than in the paracetamol group [13].

Good results have been observed when using ketoprofen in dentistry. J. Olson N. et al. conducted a study in which 239 patients were prescribed a minimum dose of ketoprofen (25 mg), ibuprofen 400 mg or paracetamol 1000 mg after extraction of the 3rd molar; The “passive” control was placebo. The main evaluation method was to compare the number of patients who were completely free of pain 6 hours after tooth extraction. This result was achieved in almost all patients who received ketoprofen - 99%, in 96% of those who received ibuprofen and 88% - paracetamol (the difference is not significant). All active drugs were superior to placebo, which relieved pain in only one third of patients (33.6%). As can be seen, even a minimal dose of ketoprofen provides the same pronounced (and even slightly greater) pain relief as standard therapeutic doses of ibuprofen and paracetamol [14].

A successful demonstration of the benefits of ketoprofen was the work of I. Jokhio et al., who compared it with diclofenac in 180 patients experiencing severe pain (average VAS value ~70 mm) due to trauma or acute soft tissue pathology of a rheumatic nature. In this case, the so-called “stepped” therapy: on the first day, NSAIDs were administered as intramuscular injections and then orally. Accordingly, half of the patients received two injections of ketoprofen 100 mg each, and then took this drug 100 mg 2 times a day. The second group of patients received two injections of diclofenac 75 mg, and subsequently took it 50 mg 3 times a day orally. The course of treatment was 2 weeks. By the end of the observation period, ketoprofen showed better results (Fig. 1). At the same time, 72% of patients receiving ketoprofen rated its tolerability as “good or excellent”; Only 50% of patients gave this assessment to diclofenac [15].

One of the latest evidence of the high analgesic effectiveness of ketoprofen was the work of Italian scientists P. Sarzi-Puttini et al. — a meta-analysis of 13 RCTs (n = 898), which compared the effect of ketoprofen 50–200 mg/day with ibuprofen 600–1800 mg/day or diclofenac 75–100 mg/day in patients with various rheumatic diseases. Ketoprofen showed significant superiority over comparator drugs in 9 of 13 RCTs. Moreover, the likelihood of achieving a favorable effect when prescribing ketoprofen was almost 2 times higher (OR 0.459: 0.33–0.58, p = 0.000) [16].

Ketoprofen has proven to be an effective remedy for relieving a migraine attack. According to the results of a study by M. Dib et al., it was not inferior to zolmitriptan, a representative of the group of triptans, which are the most important pathogenetic agent for the treatment of this disease. In this study, 235 patients with migraine took a single dose of ketoprofen 75 or 150 mg or zolmitriptan. All groups showed almost the same result: after 2 hours, pain stopped in 62.6%, 61.6% and 66.8% of patients, respectively [17].

It should be noted that ketoprofen has good anti-inflammatory potential. The best model for assessing the anti-inflammatory effect of NSAIDs is the relief of gouty arthritis, in which severe pain is determined by an acute inflammatory response. Indomethacin, which has pronounced anti-inflammatory properties, has long been considered the “gold standard” for the treatment of this pathology. Ketoprofen, as shown by R. Altman et al., was successfully compared with this drug. In the study, 59 patients with acute gouty arthritis took ketoprofen 100 mg 3 times a day or indomethacin 50 mg 3 times a day for 7 days. Ketoprofen provided significant pain relief on the first day of treatment in 92% of patients; in the control group they were 91%. After a week of treatment, the attack was completely stopped in 24% and 22% of patients. As can be seen, ketoprofen was not inferior to indomethacin in effectiveness. But at the same time, it was clearly superior in safety - while taking indomethacin, any side effects were noted in 20% of patients, and in the ketoprofen group - only in 11% [18].

In addition to emergency pain relief, ketoprofen has proven to be effective for long-term pain control in chronic musculoskeletal diseases.

Important evidence of the merits of ketoprofen was a European prospective open study that included about 20 thousand patients with various rheumatic pathologies, mainly osteoarthritis (OA). After 1 month, more than 70% of patients taking ketoprofen at a dose of 200 mg/day reported good or excellent results; At the same time, gastrointestinal complications occurred in a total of 13.5%, and ulcers and bleeding in only 0.03% [19].

The work of M. Schattenkirchner et al. showed good tolerability of ketoprofen with long-term use. In their study, 823 patients with OA and rheumatoid arthritis received ketoprofen for a year. During treatment, complications from the gastrointestinal tract occurred in 28% of patients (only 1.7% were serious), and from the cardiovascular system - in 3.2%, which is relatively small, given the predominantly elderly age of the patients and severe comorbid background [20].

Successful results were obtained when using ketoprofen in patients with ankylosing spondylitis (AS). In AS, NSAIDs play the role of the main therapeutic agent to control the progression of the disease. In a study by M. Dougados et al. 246 patients with AS took celecoxib 200 mg, ketoprofen 200 mg or placebo for 6 weeks. There was no significant difference in the analgesic effect of both NSAIDs, although they were significantly superior to placebo. Of particular interest is the effect of NSAIDs on symptoms such as night pain and morning stiffness, which largely reflect an anti-inflammatory effect. The effects of ketoprofen and celecoxib were practically the same: the reduction in night pain averaged 21 and 27 mm VAS (in the placebo group it increased by 13 mm), morning stiffness decreased by 16 and 17 minutes (it did not change in the placebo group). Thus, ketoprofen has a clear anti-inflammatory effect in AS. Interestingly, the number of gastrointestinal complications while taking coxib and ketoprofen did not differ: they occurred in 13% and 14% of patients (8% on placebo) [21]. When discussing the safety of ketoprofen, one cannot ignore the fact that a number of population-based studies demonstrate a significant risk of gastrointestinal complications for this drug. Thus, J. Castellsague et al. conducted a meta-analysis of 28 epidemiological studies (1980–2011), which assessed the development of gastrointestinal complications when using various NSAIDs. The lowest risk was observed for celecoxib - OR 1.45, aceclofenac 1.4 and ibuprofen - 1.84. The danger was significantly higher when using diclofenac - 3.34, meloxicam - 3.47 and nimesulide - 3.83. Ketoprofen was among the top three drugs with the highest risk - 3.92, as well as naproxen - 4.1 and indomethacin - 4.14 [22].

On the other hand, one of the largest population studies showed a relatively low risk of gastrointestinal complications for ketoprofen. This work by Finnish scientists A. Helin-Salmivaara et al., based on an assessment of the causes of 9191 cases of gastrointestinal bleeding, ulcers and perforation, noted from 2000 to 2004. The control group consisted of 41,780 individuals matched by gender and age. The risk of gastrointestinal complications when using ketoprofen was lower compared to diclofenac: OR 3.7 and 4.2, respectively. Interestingly, ketoprofen showed a similar or even lower risk of developing gastrointestinal pathology than more selective NSAIDs (with the exception of celecoxib). Thus, the OR for meloxicam, nimesulide and etoricoxib was 3.4, 4.0 and 4.4, respectively [23].

It should be noted that Russia has accumulated extensive experience in the use of ketoprofen. In particular, a number of clinical studies were conducted in our country, the results of which showed not only the good therapeutic potential of this drug, but also a low incidence of complications [24, 25].

Among them, the work of L. B. Lazebnik et al. should be highlighted, in which a 3-month comparison of 4 NSAIDs: lornoxicam, nimesulide, celecoxib and ketoprofen was carried out in 132 patients with OA. The authors studied the risk of gastrointestinal complications and daily dynamics of blood pressure (BP). Ketoprofen demonstrated good tolerability: the number of patients with erosions and ulcers after using lornoxicam was 66% (!), nimesulide - 13.5%, ketoprofen - 13.0%, celecoxib - 8.3%. Increased blood pressure over 130/90 mm Hg. Art. was noted in only 2% of patients receiving ketoprofen. With regard to lornoxicam and nimesulide, the situation was completely different: in patients taking these drugs, an increase in blood pressure was noted in 11% and 13% [26] (Fig. 2). This work shows one of the most valuable advantages of ketoprofen - the relatively low risk of cardiovascular complications.

The association between ketoprofen use and CV accidents has been determined in several epidemiological studies. Thus, the low risk of MI when using ketoprofen was shown by American scientists G. Singh et al. Having analyzed the causes of 15,343 episodes of myocardial infarction (61,372 people constituted the corresponding control), the authors compared the frequency of this complication in people taking NSAIDs. It turned out that taking ketoprofen was associated with the lowest risk of MI (OR 0.88), even in comparison with naproxen (OR 1.08), which is traditionally considered the safest drug in relation to CV events [27].

Similar results were obtained by M. Solomon et al., who compared the use of various NSAIDs in 4425 patients who developed MI and 17,700 individuals without this complication. According to the data obtained, there was no difference in the intake of ketoprofen in these groups: 53 patients who developed MI (1.2%) and 190 control subjects (1.1%) received it. Thus, the use of ketoprofen, according to this study, did not increase the risk of developing HF accidents [28].

A low risk of CV complications for ketoprofen was also shown by the results of a population study by Finnish scientists A. Helin-Salmivaara et al. Their work was based on a comparison of data on NSAID use in 33,309 post-MI patients and 138,949 healthy people. It turned out that taking ketoprofen did not actually increase the risk of developing HF accidents (OR 1.11) [29].

In 2012, a large-scale study was published by scientists from Taiwan who studied the CV risk when using various NSAIDs in their own population. The study material was obtained using data from the national health system, which had information on 13.7 million people who used NSAIDs, of whom 8354 had a myocardial infarction. Oral ketoprofen showed minimal risk (OR 1.17). It was found to be safer than the vast majority of other NSAIDs (Figure 3).

It should be noted that parenteral use of NSAIDs (this was a separate section of the analysis) was associated with a higher risk of LE complications. Thus, for ketoprofen the risk was more than doubled: OR 2.34; a similar value was obtained for diclofenac: 1.88, and a significantly higher value for ketorolac: 4.27 [30].

Thus, ketoprofen is a universal analgesic that can be successfully used for both acute and long-term control of chronic pain. Favorable pharmacological properties determine its advantages in comparison with other NSAIDs for urgent pain relief, when the speed of relief of suffering is of fundamental importance. The presence of different dosage forms in the doctor’s arsenal helps when choosing an analgesic therapy strategy: to obtain the fastest possible effect in the first days of treatment, the use of parenteral forms of ketoprofen may be justified, followed by a transition to regular oral administration. A positive point is also the presence on the pharmacological market of high-quality and inexpensive generics of ketoprofen, such as Flamax® (Sotex), available to most patients.

Of course, ketoprofen is not without its drawbacks; the main one, typical of all “traditional” NSAIDs, is the possibility of developing gastrointestinal pathology. However, careful consideration of risk factors before prescribing NSAIDs and, if relevant factors are present, prophylactic use of gastroprotectors (proton pump inhibitors) can significantly reduce this danger. But at the same time, ketoprofen shows a low risk of complications from the cardiovascular system. This is an undoubted advantage that expands the possibility of using this drug in elderly people, many of whom have cardiovascular risk factors.

Literature

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13. Karvonen S., Salomäki T., Olkkola K. Efficacy of oral paracetamol and ketoprofen for pain management after major orthopedic surgery // Methods Find Exp Clin Pharmacol. 2008, 30(9): 703–706.
14. J. Olson N., Otero A., Marrero I. et al. Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain // Clin Pharmacol. 2001, 41(11): 1238–1247.
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16. Sarzi-Puttini P., Atzeni F., Lanata L., Bagnasco M. Efficacy of ketoprofen vs. ibuprofen and diclofenac: a systematic review of the literature and meta-analysis // Clin Exp Rheumatol. 2013 Sep-Oct; 31 (5): 731–8. Epub 2013 May 17.
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18. Altman R., Honig S., Levin J., Lightfoot R. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol. 1988, 15(9): 1422–1426.
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A. E. Karateev, Doctor of Medical Sciences, Professor

FSBI NIIR named after. V. A. Nasonova RAMS, Moscow

Contact Information

Instructions for use KETOPROFEN-LF

Avoid using the drug in combination with other NSAIDs, incl. with selective COX-2 inhibitors.

The severity of side effects can be reduced by using the minimum effective dose for the minimum time required to improve the condition.

Elderly patients are more likely to experience adverse reactions to NSAIDs, especially GI bleeding and perforation, which can be life-threatening.

Gastrointestinal bleeding, ulcer formation or perforation, in some cases with fatal outcome, have been reported for all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal pathology. According to epidemiological data, the use of ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, which is typical for some other NSAIDs, especially when taken in high doses.

The risk of gastrointestinal bleeding, ulcer formation or perforation increases with increasing doses of NSAIDs in patients with a history of ulcers, especially those complicated by bleeding or perforation, as well as in elderly patients. In this case, treatment begins with a minimum dose. For these patients, as well as for patients taking low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, combination therapy with protective drugs, such as misoprostol or proton pump inhibitors, should be considered. Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual symptoms to the physician, especially during the initial stages of treatment. The drug should be prescribed with extreme caution to patients concomitantly receiving medications that may increase the risk of ulcers or bleeding:

• oral corticosteroids, anticoagulants (eg, warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin.

If gastrointestinal bleeding develops, use of the drug should be discontinued. NSAIDs are prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), because Exacerbations of these diseases may occur. The relative risk of developing gastrointestinal bleeding increases in patients with low body weight; if bleeding develops, treatment should be discontinued immediately.

Patients with hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and counseling as fluid retention and edema have been reported with the use of NSAIDs. According to the results of clinical studies and epidemiological data, the use of some NSAIDs, especially in high doses and for a long time, may be accompanied by an increased risk of arterial thrombosis, such as myocardial infarction or stroke. There is insufficient data to exclude such a danger when using ketoprofen.

Patients with bronchial asthma in combination with chronic allergic rhinitis, chronic allergic sinusitis and/or nasal polyps are at high risk of allergy to aspirin and/or NSAIDs. The use of ketoprofen may cause asthma attacks or bronchospasm, especially in patients with an allergy to aspirin or NSAIDs.

It is necessary to monitor renal function at the beginning of treatment in patients with heart failure, cirrhosis and impaired liver function, especially in patients receiving diuretics, patients with chronic renal failure, especially in elderly patients. In these patients, ketoprofen may cause a decrease in renal blood flow by inhibiting prostaglandins and lead to renal failure.

In patients with impaired liver function, the activity of hepatic transaminases should be regularly assessed, especially during long-term therapy. Treatment should be discontinued if visual disturbances such as blurred vision occur. Prescribe with caution to persons suffering from alcohol dependence.

Extremely rare cases of the development of serious skin reactions (some with fatal outcomes) have been described due to the use of NSAIDs, incl. exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients are at greatest risk in the first month of treatment. If a skin rash, signs of damage to the mucous membranes or other symptoms of hypersensitivity appear, the drug should be discontinued.

With prolonged treatment, it is necessary to monitor the number of blood cells, as well as liver and kidney function.

Like other NSAIDs, ketoprofen, due to its anti-inflammatory, antipyretic or analgesic effect, can mask symptoms of infection progression, such as increased body temperature.

Before major surgery, the drug must be discontinued. In case of hyperkalemia due to diabetes mellitus or concomitant therapy with potassium-sparing drugs, it is necessary to regularly monitor potassium levels.

For severe pain, ketoprofen can be used in combination with morphine.

Therapy with the injectable form of ketoprofen should be carried out under close medical supervision. When eliminating acute pain, it is advisable to switch to other dosage forms that are less likely to cause serious adverse reactions. IM administration for a long time is recommended to be carried out in a hospital under the supervision of a physician.

Excipients

The solution contains about 8% ethanol by volume, i.e. up to 197.2 mg/ampule of ethanol, which corresponds to 4 ml of beer or 1.6 ml of wine. The drug may have a negative effect on persons suffering from alcoholism. The ethanol content should be taken into account when prescribing the drug during pregnancy and lactation, children and patients at risk, for example, with liver diseases, as well as those suffering from epilepsy.

Propylene glycol in doses of 400 mg/kg for adults may cause symptoms similar to those caused by alcohol consumption.

The drug contains sodium in an amount of less than 1 mmol/ampoule and is therefore considered sodium-free.

Use in pediatrics

Use in children is contraindicated.

Due to the benzyl alcohol content, the drug should not be administered to premature infants or newborns; benzyl alcohol can cause toxic and anaphylactoid reactions in children under 3 years of age.

Propylene glycol at a dose of 200 mg/kg in children can cause symptoms similar to those caused by alcohol consumption.

Impact on the ability to drive vehicles and operate machinery

Patients should be warned that this drug may cause drowsiness, dizziness, or seizures and advised not to drive or operate machinery if these symptoms occur.

Patients should be warned about the possible occurrence of visual impairment. In this case, you should not drive vehicles or operate machinery.