Ketonal injections are an effective drug for pain relief

Ketonal injections are a popular medication in the complex treatment of diseases of the musculoskeletal system. The medicine belongs to the group of non-steroidal anti-inflammatory drugs. The solution in ampoules is used for intramuscular and intravenous administration.

Composition and indications

The main active ingredient in the drug is ketoprofen. Ketonal ampoules contain 2 ml of solution with 100 mg of active substance. The injection liquid may be clear or have a slightly yellowish tint.

Ketoprofen has anti-inflammatory, analgesic and antipyretic properties. It is quickly absorbed from the gastrointestinal tract, which causes quick results.

Ketonal injections are indicated in the treatment of various diseases for the symptomatic treatment of disease processes. They are most effective for relieving pain that accompanies inflammatory and degenerative diseases of the musculoskeletal system.

Ketonal injections, the instructions for use confirm this, improve the condition of rheumatoid and seronegative arthritis during exacerbation of diseases when severe pain occurs.

For symptomatic treatment, the drug is also prescribed:

• For gout. With the development of this disease, uric acid salts are deposited in the joints, which causes their modification and severe pain. Ketonal injections are indicated to relieve an attack of gout, which is characterized by swelling in the area of ​​one of the joints and pressing pain in it.
• For osteoarthritis. As a rule, the cause of the pathology is damage to the joint or an inflammatory process in it. Ketonal injections can relieve pain and maintain joint mobility.

Ketonal injections are prescribed to relieve post-traumatic and postoperative pain syndrome. Thanks to its pronounced analgesic properties, the drug improves the condition of cancer, algodisminorrhea, and inflammation of the pelvic organs. It can be used to relieve severe headaches caused by various reasons, as well as in other pathological conditions:

• Migraine.
• Myalgia.
• Bursitis.
• Radiculitis.
• Neuralgia.

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

1. Nasonov E. L. Analgesic therapy in rheumatology: a journey between Scylla and Charybdis // Klin. Pharmacol. therapy. 2003; 12 (1): 64–69.
2. Pain (a practical guide for doctors). Ed. Yakhno N.N., Kukushkina M.L.M.: Publishing house of the Russian Academy of Medical Sciences, 2012. 512 p.
3. Lee Y. Effect and treatment of chronic pain in inflammatory arthritis // Curr Rheumatol Rep. 2013; 15 (1): 300.
4. Karateev A. E., Yakhno N. N., Lazebnik L. B. et al. The use of non-steroidal anti-inflammatory drugs. Clinical recommendations. M.: IMA-PRESS, 2009. 167 p.
5. Varas-Lorenzo C., Riera-Guardia N., Calingaert B. et al. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysis of observational studies // Pharmacoepidemiology and Drug Safety. 2013; 22:559–570.
6. Veys E. 20 years' experience with ketoprofen // Scand J Rheumatol Suppl. 1991; 90: Suppl 1–44.
7. Sarzi-Puttini P., Atzeni F., Lanata L. et al. Pain and ketoprofen: what is its role in clinical practice? // Reumatismo. 2010, 62(3): 172–188.
8. Venegoni M., Da Cas R., Menniti-Ippolito F., Traversa G. Effects of the European restrictive actions concerning nimesulide prescription: a simulation study on hepatopathies and gastrointestinal bleedings in Italy // Ann Ist Super Sanita. 2010; 46 (2): 153–157.
9. Kokki H. Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients // Paediatr Drugs. 2010; 12 (5): 313–329.
10. Díaz-Reval M., Ventura-Martínez R., Déciga-Campos M. et al. Evidence for a central mechanism of action of S-(+)-ketoprofen // Eur J Pharmacol. 2004; 483(2–3):241–248.
11. Barden J., Derry S., McQuay H., Moore R. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults // Cochrane Database Syst Rev. 2009, Oct 7; (4): CD007355.
12. Glina S., Damiao R., Afif-Abdo J. et al. Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial // Int Braz J Urol. 2011; 37(6):697–705.
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.
15. Jokhio I., Siddiqui K., Waraich T. et al. Study of efficacy and tolerance of ketoprofen and diclofenac sodium in the treatment of acute rheumatic and traumatic conditions // J Pak Med Assoc. 1998; 48: 373–376.
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.
17. Dib M., Massiou H., Weber M. et al. Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical trial // Neurology. 2002, 58(11): 1660–1665.
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.
19. Le Loet X. Safety of ketoprofen in the elderly: a prospective study on 20,000 patients // Scand J Rheumatol Suppl. 1989; 83:21–27.
20. Schattenkirchner M. Long-term safety of ketoprofen in an elderly population of arthritic patients // Scand J Rheumatol Suppl. 1991; 91:27–36.
21. Dougados M., Béhier J., Jolchine I. et al. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug // Arthritis Rheum. 2001, 44(1):180–185.
22. Castellsague J., Riera-Guardia N., Calingaert B. et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project) // Drug Saf. 2012; 35(12):1127–1146.
23. Helin-Salmivaara A., Saarelainen S., Gronroos J. et al. Risk of upper gastrointestinal events with the use of various NSAIDs: A case-control study in a general population // Scan J Gastroenterol. 2007; 42:923–932.
24. Chichasova N.V., Immametdinova G.R., Karateev A.E. et al. Efficacy and safety of ketoprofen (ketonal) for rheumatoid arthritis (clinical and endoscopic study) // Scientific and practical rheumatology. 2001; 1; 47–52.
25. Osipova N. A., Petrova V. V., Ermolaev P. M., Beresnev V. A. Nonsteroidal anti-inflammatory drugs in the treatment of postoperative pain in cancer patients // Pharmateka. 2006, no. 6, 121.
26. Lazebnik L. B., Drozdov V. N., Kolomiets E. V. Comparative effectiveness and safety of ketoprofen, lornoxicam, nimesulide and celecoxib in patients with osteoarthritis // RMJ. 2004, 12 (14), 844–847.
27. Singh G., Mithal A., Triadafilopoulos G. Both selective COX-2 inhibitors and non-selective NSAIDs increase the risk of acute myocardial infarction in patients with arthritis; selectivity is with patients, not the drug // Ann Rheum Dis. 2005, 64 (suppl 3), 85.
28. Solomon D., Glynn R., Levin R., Avorn J. Nonsteroidal Anti-inflammatory Drug Use and Acute Myocardial Infarction. Arch Intern Med. 2002; 162:1099–1104
29. Helin-Salmivaara A., Virtanen A., Vesalainen R. et al. NSAID use and the risk of hospatalization for first myocardial infarction in the general population: a national case-control study from Finland // Eur Heart J. 2006; 27:1657–1663.
30. Shau ​​W., Chen H., Chen S. et al. Risk of new acute myocardial infarction hospitalization associated with the use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case-crossover study of Taiwan's National Health Insurance claims database and review of current evidence // BMC Cardiovasc Disord. 2012, Feb 2; 12: 4. doi: 10.1186/1471–2261–12–4.

A. E. Karateev, Doctor of Medical Sciences, Professor

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

Contact Information

Contraindications

A contraindication to ketonal injections is hypersensitivity to the active ingredient or other non-steroidal anti-inflammatory drugs, as well as salicylates.

It is prohibited to use ketonal injections in many other cases. All of them are indicated in the instructions for use of the drug. Injections with the drug are not prescribed until the age of 15 years, in the third trimester of pregnancy and during lactation.

Main contraindications of the drug:

• Exacerbation of peptic ulcer of the stomach and duodenum.
• Heart, liver and kidney failure.
• Blood clotting disorders.

You should stop using the drug if you are diagnosed with Crohn's disease and ulcerative colitis, or if you suspect gastrointestinal or other bleeding. Ketonal injections are not prescribed; the instructions warn about this after coronary artery bypass surgery.

Ketoprofen solution for intravenous and intramuscular administration 50 mg/ml 2 ml No. 10

Interaction

Undesirable combinations of drugs
with other NSAIDs
(including selective cyclooxygenase-2 inhibitors), salicylates
is not recommended , due to an increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.

Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel)

increases the risk of bleeding. If the use of such a combination is unavoidable, the patient's condition should be carefully monitored.

When used simultaneously with lithium preparations

it is possible to increase the concentration of lithium in the blood plasma up to toxic values. The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium preparations should be promptly adjusted during and after treatment with NSAIDs.

Increases hematological toxicity of methotrexate

, especially when used in high doses (more than 15 mg per week). The time interval between stopping or starting therapy with ketoprofen while taking methotrexate should be at least 12 hours.

Combinations to use with caution

During therapy with ketoprofen, patients taking diuretics

, especially if dehydration develops, have a higher risk of developing renal failure due to decreased renal blood flow caused by inhibition of prostaglandin synthesis. Before starting to use ketoprofen in such patients, rehydration measures should be carried out. After starting treatment, it is necessary to monitor kidney function.

Combined use of the drug with
ACE inhibitors and angiotensin II receptor blockers
in patients with impaired renal function (with dehydration, elderly patients) can lead to worsening deterioration of renal function, incl. to the development of acute renal failure.

During the first weeks of simultaneous use of ketoprofen and methotrexate

at a dose not exceeding 15 mg/week, blood tests should be monitored weekly. In elderly patients or if any signs of renal impairment occur, the study should be performed more frequently.

Combinations to take into account

Ketoprofen may weaken the effect of antihypertensive drugs (beta blockers, angiotensin-converting enzyme inhibitors, diuretics).

Concomitant use with
selective serotonin reuptake inhibitors (SSRIs)
increases the risk of gastrointestinal bleeding.

Concomitant use with thrombolytics

increases the risk of bleeding.

Concomitant use with potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim

increases the risk of developing hyperkalemia.

When used simultaneously with cyclosporine, tacrolimus

there may be a risk of additive nephrotoxicity, especially in elderly patients.

Use of several antiplatelet drugs (tirofiban, eptifibarid, abciximab, iloprost)

increases the risk of bleeding.

Increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.

Ketoprofen may enhance the effect of oral hypoglycemic and some anticonvulsants (phenytoin).

Concomitant use with probenecid

significantly reduces the clearance of ketoprofen in blood plasma.

Nonsteroidal anti-inflammatory drugs may reduce the effectiveness of mifepristone.

NSAIDs should be started no earlier than 8-12 days after mifepristone is discontinued.

Pharmaceutically incompatible with tramadol

due to precipitation.

Use during pregnancy

According to studies, ketaprofen can have a negative effect on the general course of pregnancy and provoke spontaneous abortion. In addition, when taking the drug there is a risk of developing intrauterine pathologies of the fetus. At the same time, the likelihood of negative consequences for the mother and unborn child increases depending on the dose and duration of use of the drug.

Ketanol injections are prescribed in the first and second trimesters only in cases where the benefits to the woman outweigh the possible risks to the fetus. In this case, the minimum effective dose is indicated, which is taken in a short course.

Absolute contraindications to taking the drug in the third trimester are explained by the fact that ketanol injections can lead to the possible development of weakness of the uterus and other pathological conditions. In addition, even small doses of the drug during this period of pregnancy can increase the duration of bleeding and have a negative effect on the fetus. The use of ketanol injections during lactation is attributed to the fact that studies on whether ketaprofen gets into breast milk and its effect on the child have not been conducted.

Side effects and overdose

Ketonal injections, the instructions for use warn about this, can cause serious negative side reactions of the body from various systems of the human body. You should carefully read the manufacturer's warnings before using the product for symptomatic treatment.

The most common side effects are insomnia, depression, and asthenia. Nervous system disorders may be accompanied by headaches and increased weakness. Also, after taking the medicine, dyspeptic disorders often occur.

An overdose of ketoprofen poses a health risk. Higher doses may cause vomiting and abdominal pain. The drug, used once in large quantities, can lead to respiratory depression, convulsions, and loss of consciousness. There are risks of developing renal dysfunction. If an overdose is confirmed, you urgently need to rinse your stomach and take absorbents. Further symptomatic treatment is recommended.

Ketonal injections, which are affordable, interact with many other medications. Therefore, it is strictly forbidden to use them for self-medication. Dosages are prescribed by the doctor depending on the patient’s condition and in accordance with the recommendations of the instructions for use.

Ketoprofen

Directions for use and doses

Intravenously (drip), intramuscularly.

To achieve the frequency of adverse reactions, it is recommended to use the minimum effective dose of the drug. The maximum daily dose is 200 mg.

It is necessary to carefully evaluate the ratio of expected benefits and risks before starting to take Ketoprofen at a dose of 200 mg/day.

Intramuscular administration.

Intramuscularly 100 mg 1-2 times a day. Ketoprofen is injected deeply, slowly into the upper outer square of the buttock, under strictly aseptic conditions. Subsequent injections are administered alternately into both buttocks.

Intravenous administration. Intravenous infusion of Ketoprofen should be carried out only in a hospital setting.

Short intravenous infusion: 100 to 200 mg of Ketoprofen is diluted in 100 ml of 0.9% sodium chloride solution and administered over 0.5-1 hour; administration can be repeated every 8 hours for no more than 48 hours.

Continuous intravenous infusion: from 100 to 200 mg of Ketoprofen is diluted in 500 ml of solution for infusion (0.9% sodium chloride solution, lactated Ringer's solution, 5% dextrose solution); administered within 8 hours; administration can be repeated every 8 hours for no more than 24 hours.

Treatment with the drug should not exceed 2-3 days.

Parenteral administration of the drug, if necessary, can be combined with the use of oral forms (tablets, capsules) or rectal suppositories.

Ketoprofen can be combined with centrally acting analgesics: it can be mixed with opioids (for example, morphine) in the same vial; it is pharmaceutically incompatible with tramadol solution due to precipitation.

Elderly patients:

The minimum effective dose is recommended. Patients should be monitored regularly because... Gastrointestinal bleeding is possible during therapy with NSAIDs.

For patients with renal impairment, the minimum effective dose is recommended and then adjusted based on renal tolerability.

Due to the fact that Ketoprofen is sensitive to light, the bottle or infusion bag should be covered with black paper or aluminum foil.

Side effect

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (?1/10) often (?1/100, <1/10), infrequently (?1/1000, <1 /100), rare (?1/10000, <1/1000) and very rare (<1/10000), frequency unknown (the frequency of events cannot be determined based on the available data).

From the hematopoietic and lymphatic systems:

rarely: hemorrhagic anemia, hemolytic anemia, leukopenia;

frequency unknown: agranulocytosis, thrombocytopenia, bone marrow dysfunction.

From the immune system:

frequency unknown: anaphylactic reactions (including anaphylactic shock).

From the nervous system:

often: insomnia, depression, asthenia;

uncommon: headache, dizziness, drowsiness;

rarely: paresthesia, confusion or loss of consciousness, peripheral polyneuropathy; frequency unknown: convulsions, taste disturbances, emotional lability.

From the senses:

rarely: blurred vision, tinnitus, conjunctivitis, dry mucous membrane of the eye, eye pain, hearing loss;

frequency unknown: optic neuritis.

From the cardiovascular system:

uncommon: tachycardia;

frequency unknown: heart failure, increased blood pressure, vasodilation.

From the respiratory system:

rarely: exacerbation of bronchial asthma, nosebleeds, laryngeal edema;

frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.

From the gastrointestinal tract:

often: nausea, vomiting, dyspepsia, abdominal pain, NSAID gastropathy;

uncommon: constipation, diarrhea, bloating, gastritis;

rarely: peptic ulcer, stomatitis;

very rarely: exacerbation of ulcerative colitis, Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the gastrointestinal tract;

frequency unknown: gastrointestinal discomfort, stomach pain.

From the liver and biliary tract:

rarely: hepatitis, increased activity of liver enzymes and bilirubin.

From the skin:

uncommon: skin rash, itching;

frequency unknown: photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, purpura.

From the urinary system:

rarely: cystitis, urethritis, hematuria;

very rarely: acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values ​​of renal function indicators;

frequency unknown: fluid retention in the body and, as a result, weight gain, hyperkalemia.

Other:

uncommon: peripheral edema, fatigue;

rarely: hemoptysis, menometrorrhagia, shortness of breath, thirst, muscle twitching.

Overdose

An overdose was detected in doses greater than 2.5 g of Ketoprofen.

Symptoms

Manifest as an increase in dose-dependent side effects: convulsions, feeling of heaviness in the legs, high blood pressure, ringing in the ears, blurred vision, rash, nausea, vomiting, epigastric pain, diarrhea, gastrointestinal bleeding, headache, dizziness, incoherence (incoherence), confusion, drowsiness, convulsions, coma, respiratory depression.

Treatment

Symptomatic, no specific antidote for Ketoprofen is known. Provide appropriate hydration, monitor renal clearance, and correct acidosis. If necessary, hemofiltration is used.

Interaction with other drugs

Undesirable combinations of drugs.

The combined use of ketoprofen with other NSAIDs (including selective cyclooxygenase-2 inhibitors), salicylates in high doses is not recommended, due to the increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.

Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel) increases the risk of bleeding. If the use of such a combination is unavoidable, the patient's condition should be carefully monitored.

When used simultaneously with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma up to toxic values. The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium preparations should be promptly adjusted during and after treatment with NSAIDs.

Increases the hematological toxicity of methotrexate, especially when used in high doses (more than 15 mg per week). The time interval between stopping or starting therapy with ketoprofen while taking methotrexate should be at least 12 hours.

Combinations that must be used with caution.

During therapy with ketoprofen, patients taking diuretics, especially if dehydration develops, have a higher risk of developing renal failure due to a decrease in renal blood flow caused by inhibition of prostaglandin synthesis. Before starting to use ketoprofen in such patients, rehydration measures should be carried out. After starting treatment, it is necessary to monitor kidney function.

Combined use of the drug with ACE inhibitors and angiotensin II receptor blockers in patients with impaired renal function (with dehydration, elderly patients) can lead to worsening deterioration of renal function, incl. to the development of acute renal failure.

During the first weeks of simultaneous use of ketoprofen and methotrexate at a dose not exceeding 15 mg/week, blood tests should be monitored weekly. In elderly patients or if there are any signs of renal impairment, the study should be performed more frequently.

Combinations to take into account.

Ketoprofen may weaken the effect of antihypertensive drugs (beta blockers, angiotensin-converting enzyme inhibitors, diuretics).

Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.

Concomitant use with thrombolytics increases the risk of bleeding.

Concomitant use with potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of developing hyperkalemia.

When used simultaneously with cyclosporine and tacrolimus, there may be a risk of additive nephrotoxicity, especially in elderly patients.

The use of several antiplatelet drugs (tirofiban, eptifibarid, abciximab, iloprost) increases the risk of bleeding.

Increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.

Ketoprofen may enhance the effect of oral hypoglycemic and some anticonvulsants (phenytoin).

Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.

Nonsteroidal anti-inflammatory drugs may reduce the effectiveness of mifepristone. Taking NSAIDs should be started no earlier than 8-12 days after stopping mifepristone.

Pharmaceutically incompatible with tramadol solution due to precipitation.

special instructions

With long-term use of NSAIDs, it is necessary to periodically evaluate a clinical blood test, as well as monitor renal and liver function, especially in elderly patients (over 65 years), and conduct a stool test for occult blood. It is necessary to be careful and monitor blood pressure more often when using ketoprofen to treat patients suffering from arterial hypertension and cardiovascular diseases that lead to fluid retention in the body.

If visual disturbances occur, treatment should be stopped immediately.

Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. If you notice signs of infection or deterioration in health while using the drug, you should immediately consult a doctor.

If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high dosages of ketoprofen, the patient should be under close medical supervision.

Because of the important role of prostaglandins in maintaining renal blood flow, particular caution should be exercised when prescribing ketoprofen to patients with cardiac or renal insufficiency, as well as when treating elderly patients taking diuretics and patients who, for any reason, have a decrease in circulating volume. blood (for example, after surgery). The use of ketoprofen can affect female fertility, therefore, patients with infertility (including those undergoing examination) are not recommended to use the drug.

The influence of a medicinal product for medical use on the ability to drive vehicles and machinery

During the period of use of the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, since the drug can cause dizziness and other side effects that can affect these abilities.