Gel, suppositories, cream, IV injections, Ketonal tablets: instructions for use, price, reviews and analogues

Compound

Solution - ketoprofen , propylene glycol, ethanol, benzyl alcohol, sterile water.
Gel - ketoprofen, trolamine, carbomer , ethanol, lavender essential oil, sterile water.
Cream - ketoprofen, isopropyl myristate, methylhydroxybenzoate, propylene glycol, propylhydroxybenzoate, white petrolatum, magnesium sulfate, elphacos ST9, propylene glycol oleate, glyceryl, water.
Tablets - silicon dioxide, magnesium stearate, talc, corn starch, lactose, macrogol , hypromellose, titanium dioxide, indigo carmine, wax, talc.
Capsules - ketoprofen, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, povidone, polysorbate, purified water, eudragit, triethyl citrate, talc, yellow iron oxide, purified water, silicon dioxide, titanium dioxide, gelatin.
Suppositories - ketoprofen, solid fat, glyceryl caprylocaprate.

Release form

Solution 50 mg/ml for intravenous and intramuscular administration - in dark glass ampoules of 2 ml, in a blister of 5 and 10 ampoules in cardboard packaging No. 10.2
Gel 2.5% - for external use, colorless, transparent, homogeneous in an aluminum tube of 50, 100 g in a cardboard package.
Cream 5% - for external use, homogeneous, white in aluminum tube, 30, 50 g in a cardboard package.
Ketonal tablets 50 mg are biconvex round, film-coated in dark glass bottles of 20 pcs. in cardboard packaging.
Capsules 50 mg with modified release - blue in blister in cardboard packaging No. 20, 30.
Rectal suppositories are smooth, white, homogeneous in a blister of 6 suppositories in a cardboard package No. 12.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Ketoprofen inhibits the activity of cyclooxygenase , which inhibits the process of prostaglandin .

The drug also inhibits the synthesis of bradykinin , lipoxygenase , stabilizes lysosomal membranes in the cell and suppresses the production of enzymes that are involved in the inflammatory process. Ketoprofen does not have a negative effect on the condition of articular cartilage.

Pharmacokinetics

The process of absorption of ketoprofen in the body is very slow and it practically does not accumulate in the body. Bioavailability - 5%. The drug penetrates well and reaches therapeutic concentrations in synovial fluid, muscles, ligaments, and subcutaneous tissue. Its concentration in blood plasma is insignificant. Metabolized in the liver to form conjugates. Excreted in urine. Slowly.

Pharmacological properties of the drug Ketonal

Pharmacodynamics. Ketoprofen is an NSAID that has analgesic, anti-inflammatory and antipyretic effects. During inflammation, ketoprofen inhibits the synthesis of prostaglandins and leukotrienes, inhibiting the activity of cyclooxygenase and partially lipoxygenase; it also inhibits the synthesis of bradykinin and stabilizes lysosomal membranes. It has an analgesic effect and eliminates the manifestations of symptoms of inflammatory and degenerative diseases of the musculoskeletal system. Pharmacokinetics. When taken orally, ketoprofen is rapidly absorbed into the gastrointestinal tract. After oral administration (50 mg 4 times a day) with meals, the maximum concentration of ketoprofen in the blood plasma is reached after 1.5 hours and is 3.9 mcg/ml, whereas when taken on an empty stomach it is 2.0 mcg/ml and is achieved after 2 hours; for extended-release tablets, the maximum concentration in the blood plasma is achieved after 4–6 hours. The bioavailability of ketoprofen in oral forms is 90–93% and is directly proportional to the dose that is used. After rectal administration of 100 mg of ketoprofen, the maximum concentration in blood plasma (10.4 μg/ml) is determined after 1.05–1.22 hours. The bioavailability of ketoprofen is 71–96%. With intravenous infusion, the average level in blood plasma 5 minutes from the start and 4 minutes after completion of the administration is 26.4 ± 5.4 μg/ml. Bioavailability is 90%. The degree of protein binding is 99%. Volume of distribution - 0.1–0.2 l/kg. Ketoprofen penetrates into the synovial fluid. A stable concentration of ketoprofen in the blood plasma is achieved within 24 hours after taking oral forms. The pharmacokinetics of ketoprofen do not differ significantly depending on the age of the patients. Cumulation of ketoprofen in tissues is not observed. Ketoprofen is extensively metabolized in the liver via microsomal oxidation. It is excreted from the body in the form of a conjugate with glucuronic acid. The half-life is 2 hours. Up to 80% of the administered dose of ketoprofen is excreted in the urine, usually (over 90%) in the form of glucuronide, about 10% in feces. In patients with renal failure, the elimination of ketoprofen is slowed down, the half-life increases by 1 hour. In patients with liver failure, ketoprofen may accumulate in tissues. In elderly patients, the metabolism and excretion of ketoprofen is slow, but this is of clinical significance only in cases of impaired renal function.

Indications for use

Indications for use of various forms of the drug are identical. The choice of the form of release of the drug is based on a number of factors (type of disease, ease of administration).

The drug is prescribed in the following cases:

Symptomatic treatment of inflammatory and degenerative diseases of the musculoskeletal system ( arthritis of various origins, osteochondrosis , osteoarthritis , gout , articular and non-articular rheumatism , myalgia , tendonitis , bursitis , neuralgia , glenohumeral syndrome, injuries of the musculoskeletal system - sprains and ruptures of ligaments, muscle bruises )
Relief of pain syndrome in myalgia, bursitis, tendinitis, neuralgia, radiculitis, migraine , headache, algodismenorrhea , renal colic, post-traumatic pain syndrome, cancer, adnexitis , lumbago , lymphadenitis and lymphangitis , phlebitis .

Contraindications

Individual hypersensitivity to the drug and other NSAIDs, bleeding disorders, childhood, liver/renal failure , chronic dyspepsia , exacerbation of peptic ulcer , ulcerative colitis , period after surgery, lactation and during pregnancy in the 3rd trimester.

Prescribe with caution if there is a history of bronchial asthma , peptic ulcer; diabetes mellitus , arterial hypertension , simultaneous use of anticoagulants , cardiovascular diseases, long-term treatment with NSAIDs, in old age.

Special instructions for the use of the drug Ketonal

When prescribing Ketonal for systemic use, caution should be exercised in patients with a history of gastric or duodenal ulcers or gastrointestinal bleeding. Perforation or gastrointestinal bleeding may occur without the development of previous symptoms. Caution is recommended in patients with impaired liver or kidney function, as well as in patients taking coumarin anticoagulants. The drug is not recommended for use in porphyria. If renal function is impaired, dose adjustment is necessary. Ketoprofen may worsen the course of hypertension (arterial hypertension) and increase the risk of developing peripheral edema. Ketoprofen should be prescribed with caution to elderly people due to the increased risk of side effects. As with the treatment of other NSAIDs, with long-term use of ketoprofen it is necessary to monitor the composition of peripheral blood, liver and kidney function, especially in the elderly. Like other NSAIDs, ketoprofen may mask symptoms and signs of infectious diseases. Smoking and drinking alcohol are not recommended during treatment with Ketonal. The safety of using ketoprofen during pregnancy and lactation has not been established. Ketoprofen can be used in the first and second trimesters of pregnancy only if the expected therapeutic effect for the expectant mother exceeds the potential risk to the fetus. NSAIDs are not recommended for use during pregnancy beyond 36 weeks. When treating with Ketonal, you must stop breastfeeding. The drug does not affect the ability to drive vehicles or operate potentially dangerous machinery. However, in rare cases, NSAIDs may cause dizziness or drowsiness. In this case, you should refuse to manage such funds.

Side effects

Side effects of the drug can manifest as disturbances in different body systems:

anaphylactic reactions;
anemia , leukopenia , thrombocytopenia , agranulocytosis , bone marrow function disorders;
asthenia , insomnia, depression , drowsiness, dizziness, headache, convulsions, confusion;
tinnitus, eye pain, blurred vision, conjunctivitis , hearing loss;
tachycardia , increased blood pressure, heart failure;
nosebleeds, bronchospasm , rhinitis , laryngeal edema ;
nausea, dyspepsia , pain in the abdomen, gastritis , constipation , diarrhea ;
hepatitis;
skin itching and rash, photosensitivity;
urethritis , cystitis , hematuria ;
peripheral edema, fatigue;
weight gain, thirst, shortness of breath .

Side effects of the drug Ketonal

As usual, transient. Most often, gastrointestinal disorders are observed (digestive disorders, dyspepsia, nausea, vomiting, constipation, diarrhea, heartburn, abdominal pain). Rarely - headache, dizziness, confusion, hypersomnia, drowsiness, swelling, mental changes, insomnia. In isolated cases, possible ulcerative stomatitis, ground, hematemesis, peptic ulcer, gastrointestinal hemorrhage or perforation, gastritis, duodenal and stomach ulcers. From the blood system: rarely - anemia, hemolysis, purpura, thrombocytopenia, agranulocytosis. High doses of ketoprofen can inhibit platelet aggregation, thereby prolonging bleeding time, and cause epistaxis and hematoma formation. From the immune system: asthma, bronchospasm or shortness of breath (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs); very rarely - angioedema and anaphylaxis. Mental disorders: common - depression, nervousness, nightmares, drowsiness; rarely - delirium with visual and auditory hallucinations, disorientation, dyslalia. From the side of the central nervous system: often - headache, asthenia, discomfort, increased fatigue, weakness, dizziness, paresthesia; very rarely - there have been isolated reports of cases of pseudotumor cerebri. From the organ of vision: often - visual impairment; very rarely - conjunctivitis. On the part of the hearing organ: common - tinnitus. From the cardiovascular system: often - edema; rarely - heart failure, hypertension (arterial hypertension). Clinical studies and epidemiological evidence suggest that a small increased risk of arterial thrombotic events (eg, myocardial infarction and stroke) may be associated with the use of some NSAIDs (especially at high doses and long-term use). There is insufficient data to exclude such a risk for ketoprofen. From the respiratory system: uncommon - hemoptysis, shortness of breath, pharyngitis, rhinitis, bronchospasm, laryngeal edema (signs of an anaphylactic reaction); rarely - asthma attacks. From the gastrointestinal tract: very - dyspepsia; often - nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting, stomatitis; very rarely - colitis, intestinal perforation (as complications of diverticula), exacerbation of ulcerative colitis or Crohn's disease, enteropathy with perforation, stenosis. Enteropathy may be accompanied by mild bleeding with loss of protein. There have been case reports of rectal perforation in elderly women. Peptic ulcers, perforation or gastrointestinal bleeding may occur, sometimes fatal, especially in elderly patients. Ulceration, hemorrhage or perforation may develop in 1% of patients after 3–6 months of treatment or in 2–4% of patients after 1 year of treatment with NSAIDs. Melena, bloody vomiting, and exacerbations of ulcerative colitis or Crohn's disease have been reported after use. Gastritis was rarely observed. From the hepatobiliary system: very rarely - severe liver dysfunction, which is accompanied by jaundice and hepatitis. Skin disorders: common - skin rash; in isolated cases - alopecia, eczema, purple-like rash, increased sweating, urticaria, exfoliative dermatitis; rarely – photosensitivity, photodermatitis; very rarely - bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. From the urinary system: very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis. From the reproductive system: very rarely - menometrorrhagia. Laboratory indicators: very often - deviation from the norm in liver function tests; rarely - during treatment with NSAIDs, ALT and AST levels increase significantly. Ketoprofen reduces platelet aggregation, thereby prolonging bleeding time.

Instructions for use of Ketonal (Method and dosage)

Ketonal tablets, instructions for use

Take 1 tablet Ketonal (50 mg) orally twice a day or Ketonal Forte (100 mg), swallowing whole and drinking at least 100 ml of liquid (water, milk) after meals.

The maximum daily dose of the drug should not exceed 200 mg per day. In this case, Ketonal tablets can be combined with other forms of the drug (cream, suppositories). You can take extended-release tablets (Ketonal Retard) - 150 mg (1 tablet) once a day.

Cream Ketonal, instructions for use

Apply a little 5% cream (3–5 cm) to the skin and lightly rub Ketonal cream 2–3 times a day into problem areas of the body. The duration of self-treatment should not exceed two weeks. If there is no effect, you should contact a specialist. Sometimes patients mistakenly say “ointment” when referring to the cream.

Gel Ketonal, instructions for use

The gel is applied similarly to the cream. The dosage of the gel must be selected in accordance with the area of the problem area. Approximate dosage - 5 cm of gel corresponds to 100 mg of Ketonal.

Ketonal capsules, instructions for use

For arthritis, dysmenorrhea, osteoarthritis and mild or moderate pain syndrome, take one capsule orally with meals, with milk or water every six hours. Can be used in combination with injection solution, suppositories, taking into account the maximum daily dose. Concomitant use with antacids .

Ketonal injections, instructions for use

For parenteral use, the drug is administered as an intramuscular injection in an amount of 100 mg 1–2 times a day. IV infusion: the procedure is carried out in a hospital setting. Short infusion - ketoprofen in ampoules (100–200 mg) is diluted in a solution of 0.9% sodium chloride (100 ml) and administered over one hour, repeated administration no earlier than eight hours later. For continuous infusion, the drug (100–200 mg) is diluted in 500 ml of Ringer's solution or 0.9% sodium chloride and administered over eight hours. Ketonal IV can be administered together with centrally acting analgesics .

Ketonal suppositories, instructions for use

Rectal suppositories are inserted into the rectum, as deeply as possible, one suppository 1-2 times a day. You can combine the administration of suppositories with oral forms of the drug (tablets, capsules).

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.

Interaction

Ketoprofen reduces the effectiveness of antihypertensive drugs and diuretics , enhances the effect of hypoglycemic oral drugs and a number of anticonvulsants ( phenytoin ).

Concomitant use with anticoagulants , antiplatelet agents and thrombolytics increases the risk of bleeding. Taking Ketonal with salicylates , other NSAIDs , ethanol and corticosteroids increases the risk of developing gastrointestinal complications.

Ketonal increases the concentration in the blood of lithium drugs , cardiac glycosides , CCBs , methotrexate , cyclosporine , and when administered simultaneously with potassium-sparing diuretics , ACE inhibitors , tacrolimus , low molecular weight heparins and trimethoprim hyperkalemia increases .

Interactions of the drug Ketonal

Ketoprofen, when used systemically, increases the effectiveness of oral hypoglycemic and some antiepileptic drugs, reduces the effectiveness of diuretics and antihypertensive drugs. The simultaneous use of diuretics and NSAIDs increases the risk of developing renal failure. The use of Ketonal with ACE inhibitors increases the risk of nephrotoxicity. Patients taking ketoprofen in combination with warfarin and corticosteroids require regular medical monitoring due to the possibility of bleeding. Treatment of patients with ketoprofen simultaneously with lithium should be carried out under close medical supervision, since the toxicity of lithium increases. When ketoprofen is taken simultaneously with methotrexate and cyclosporine, the toxicity of the latter may increase. Ketoprofen should not be taken in combination with salicylates and other NSAIDs.

Ketonal's analogs

Level 4 ATC code matches:
Voltaren Emulgel

Ultrafastin

Indomethacin

Dicloran

Dicloran Plus

Dolgit

Nise

Ketorol

Febrofeed

Fastum gel

Diclofenac

Finalgel

Bystrumgel

Deep Relief

Butadion

Diklovit

Artrosilene

Olfen

Fanigan Fast

Analogs of Ketonal in tablets and capsules - Artrum , Ketoprofen , Indomethacin , Ibuprofen , Osteoartisi Active Plus , Artron Complex , Flamax Forte , Denebol , Ketoprofen MV , Chondra-Sila , Flexen , Bystrumkaps , Oruvel , Ultrafastin , Profenid and others.

Analogues of Ketonal in the form of a solution are Artrosilene , Diclofenac , Denebol , OKI , Emodol , Oruvel , Flamax , Flexen , Chondrolone and others.

Analogs of cream and gel Ketonal - Artrosilen , Ketoprofen , Voltaren , Febrofid , Bystrumgel , F-gel , Fastum- , Ketoprom , Oruvel , Ketum-gel , Reanimator Thermo-gel , Valusal , Arthropod , Ultrafastin , Fort-gel , Profenid , Flexen .

Analogues of Ketonal in the form of suppositories are Artrum , Oruvel , Flexen , Artrosilen .

The price of analogues may differ significantly from the cost of Ketonal. When replacing the drug, you should consult a specialist.

Reviews about Ketonal

On the Internet you can find numerous reviews about Ketonal, mostly favorable. The most favorable reviews about Ketonal in tablets and injections:

“... I had a kidney stone pass, hellish pain, neither baralgin nor other analgesics helped. The emergency doctor gave Ketonal injections and the pain went away almost immediately. An excellent pain reliever, not a narcotic and affordable.”
“... I had a tooth removed. During extraction, the tooth crumbled and when they began to pull out the roots, there was hellish pain. But after the Ketonal injection I stopped feeling pain. A good cure for toothache."
“... I suffer from osteochondrosis, for which I take Ketonal tablets and use cream, it helps a lot.”

Many patients leave good reviews about Ketonal cream and often call it “ointment”: “...my mother has been using Ketonal ointment for arthrosis for quite a long time. The drug relieves pain in the knee joints well and quickly. It’s not the cheapest drug, but it’s very effective.”

There are also negative reviews: “... I ride a horse. After the fall, my ankle began to hurt severely. I used the cream for a month. It didn’t help, the joint continued to hurt. We got “horse balm” at the hippodrome – excellent results.”

Those who are not familiar with the drug ask the question: “what is Ketonal ointment for?” It is successfully used for injuries to the ligamentous apparatus and muscles, which is very important for people leading an active lifestyle. What else can the ointment be used for? Local treatment in the forms of cream, ointment, gel is very effective for inflammation of the veins (phlebitis). In this case, NSAIDs are prescribed in parallel with venotonics and thrombolytics.

Reviews about the gel are also positive, and it is noted that this dosage form is absorbed more easily and quickly, without leaving marks on the skin and clothing; the use of the gel is more economical.

There are also numerous positive reviews about suppositories in gynecology: “... For me, the beginning of the menstrual cycle is almost always accompanied by severe pain. Whatever I drank. The emergency doctor recommended Ketonal suppositories and the pain subsided. Of course, the application procedure is not very pleasant. After inserting the suppository, I feel some discomfort (slight burning and itching), but they quickly relieve the pain and the effect lasts the whole day. Excellent product."

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.

Ketonal price, where to buy

The price of Ketonal depends on the form of the drug.

The price of Ketonal in injections (ampoules 2 ml 100 mg) No. 10 varies from 230 to 305 rubles per pack; Ketonal ampoules No. 50 – 957 – 1490 rubles.

The price of Ketonal in tablets 100 mg No. 20 ranges from 200 to 210 rubles; tablets Ketonal Retard 150 mg No. 20 –235 – 302 rubles.

The cost of Ketonal in capsules 50 mg No. 25 is 105 – 115 rubles.

The price of Ketonal cream 5% in a 30 g tube varies from 230 to 297 rubles; 50 g – from 310 to 395 rubles.

The price of Ketonal gel 2.5% in a 100 g tube ranges from 338 to 466 rubles per package.

The price of Ketonal in candles No. 12 pieces varies from 283 to 345 rubles.

You can purchase medications without difficulty in most pharmacies in Moscow and other cities.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine
Online pharmacies in KazakhstanKazakhstan

ZdravCity

Ketonal cream for external use.
approx. 5% tube 100g Salutas Pharma GmbH RUB 613 order
Ketonal capsules 50 mg 25 pcs. Lek dd
110 rub. order
Ketonal cream 5% 50gLek dd/Salutas Pharma GmbH
RUR 457 order
Ketonal solution for intravenous and intramuscular administration. 50mg/ml 2ml 10 pcs. Lek dd
RUB 234 order
Ketonal tablets p.p.o. 100 mg 20 pcs Lek dd
RUB 153 order

Pharmacy Dialogue

Ketonal (amp. 50 mg/ml 2 ml No. 10)Lek
RUB 256 order
Ketonal (tab.p.pl/vol. 100 mg No. 20)Lek
160 rub. order
Ketonal cream (tube 5% 50g)Salutas Pharma GmbH
481 rub. order
Ketonal Duo (caps. 150 mg No. 30)Lek
260 rub. order
Ketonal 2.5% gel 50gSalutas Pharma GmbH
RUB 352 order

Pharmacy24

Ketonal 100 mg 2 ml No. 10 injection solution Lek pharmaceutical company d.d., Slovenia
204 UAH.order
Ketonal forte 100 mg No. 20 tablets Lek pharmaceutical company d.d., Slovenia
133 UAH order
Ketonal 100 mg No. 12 suppositories Lek pharmaceutical company d.d. Slovenia / Sandoz Ilac Sanay ve Ticaret A.S., Turecchina
149 UAH order
Ketonal retard 150 mg No. 2 tablets Lek pharmaceutical company d.d., Slovenia
182 UAH order
Ketonal 2.5% 50 g gel Salutas Pharma GmbH, Nimechchina
93 UAH order

PaniPharmacy

Ketonal capsule Ketonal capsules 50 mg No. 25 Slovenia, Lek
117 UAH. order
Ketonal suppository Ketonal suppository 100 mg No. 12 Slovenia, Lek
152 UAH order
Ketonal retard tablets Ketonal retard tablets 150 mg No. 20 Slovenia, Lek
198 UAH order
Ketonal duo capsule Ketonal DUO capsules 150 mg No. 20 Slovenia, Lek
192 UAH order
Ketonal forte tablets Ketonal forte film-coated tablets 100 mg No. 20 Slovenia, Lek
144 UAH order

Ketonal in the practice of a rheumatologist

Joint diseases are one of the most common reasons for a patient to visit a doctor (Fig. 1).
The pain syndrome accompanying damage to joints and periarticular tissues in most cases is chronic, significantly worsening the patient’s quality of life. Although there are many reasons for the appearance of pain in various structures of the musculoskeletal system: pain can be associated with damage to blood vessels or nerves, with increased intramedullary pressure, with spasm of the periarticular muscles, but most often the pain syndrome is associated with the development of chronic inflammation in the synovium
. Patients suffering from rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthropathy are often forced to take painkillers for many years, which should also have an anti-inflammatory effect. The increasing incidence of deforming osteoarthritis in the population also increases the number of patients in need of pain-relieving agents. Therefore, certain requirements are imposed on drugs that reduce inflammation and pain: the drugs must be effective and well tolerated both in the short term and over long periods of use.

Rice.
1. The incidence of various diseases in the population (US National Health Interview Survey, 1999) Nonsteroidal anti-inflammatory drugs
(NSAIDs) have three main actions - analgesic, anti-inflammatory and antipyretic.
They are widely used in medical practice, primarily for the relief of acute and chronic pain of various origins. Most drugs in this group are, by their main mechanism of action, non-selective inhibitors of the enzyme cyclooxygenase (COX), which is involved in the breakdown of phospholipids in cell membranes when cells are damaged [1], which determines their therapeutic effect (suppression of COX-2), but is also associated with the development of adverse reactions (suppression of COX-1). These provisions formed the basis for the development of a new class of NSAIDs - COX-2 selective drugs
(meloxicam, nimesulide, celecoxib), the effectiveness of which in chronic inflammatory diseases of the musculoskeletal system is well known to clinicians, and the tolerability in relation to the mucous membrane of the gastrointestinal tract (GIT) is comparable using placebo [2,3]. When using non-selective COX inhibitors, it was believed that a more pronounced analgesic or anti-inflammatory effect is necessarily associated with a higher frequency of side effects. However, in recent years, new facts have emerged about the COX-independent mechanisms of the effectiveness and toxicity of NSAIDs [4]. There have been reports that non-selective NSAIDs have a central mechanism of analgesic action, which in most cases is more pronounced than that of selective COX-2 inhibitors [5,6].

The drug ketoprofen (Ketonal)

is a derivative of propionic acid, as well as the well-known and long-known ibuprofen and flurbiprofen.
Propionic acid derivatives are the most well tolerated among other non-selective NSAIDs. Its pronounced analgesic effect is well known, exceeding that of derivatives of phenylacetic acid (diclofenac) and indoleacetic acid (indomethacin). In this regard, “a priori” it was believed that ketoprofen should also be poorly tolerated. This may be why Ketonal is more widely used by specialists dealing with the problems of acute pain syndrome - surgeons, traumatologists, dentists, gynecologists and oncologists - than by specialists - rheumatologists. In the works of P.S. Veksheva et al. [7] optimal pain relief during minor traumatic surgical interventions in 94.3% of cases was achieved with Ketonal monotherapy at a dose of 100 mg 2–3 times a day. During highly traumatic surgical interventions, the use of Ketonal made it possible to reduce the dose of narcotic analgesics [8]. A comparative study of the effectiveness of various NSAIDs in postoperative pain relief showed the advantages of Ketonal (300 mg/day IM) over diclofenac (150–200 mg/day IM) and ketorolac (90 mg/day IM) with better tolerability of Ketonal: frequency adverse effects were 4%, 31% and 14%, respectively [9,10]. Also, high efficiency and better tolerability of Ketonal compared to indomethacin and diclofenac were noted in the treatment of pain in patients with malignant tumors [11]. When using Ketonal for pain relief in gynecological practice after endoscopic interventions, it was shown that the most effective form of the drug is forte tablets compared to suppository and capsulated forms
[12].

In most cases, a rheumatologist deals with chronic joint diseases (arthritis, arthrosis), when patients are forced to continuously use NSAIDs for many months and years. The required duration of taking NSAIDs and the known fact that the frequency of adverse reactions from the gastrointestinal tract (ulcers of the gastric and duodenal mucosa, bleeding) while taking NSAIDs is higher in patients with damage to the musculoskeletal system than in those suffering from other types of chronic pain [13 ], force the doctor to look for the safest drugs. However, selective COX-2 inhibitors in some forms of inflammation have an anti-inflammatory effect only in very high doses, when the synthesis of COX-1 is also suppressed.

Ketonal belongs to the group of propionic acid derivatives, which includes the safest NSAIDs, has a short half-life (T1/2 = 1–2 hours), rapid absorption and elimination [14]. Due to its high fat solubility, Ketonal quickly penetrates the blood-brain barrier and is able to influence the transmission of pain signals at the level of the dorsal horns of the spinal cord, which determines its central mechanism of analgesic action. These pharmacodynamic characteristics of ketoprofen served as the basis for the wider use of Ketonal in rheumatological practice. We conducted clinical and clinical endoscopic studies to study the effectiveness and tolerability of Ketonal in patients with severely active rheumatoid arthritis, ankylosing spondylitis with long-term use, as well as in patients with arthrosis. A number of special clinical studies have already shown that the pharmacokinetics of Ketonal in young and elderly people does not have pronounced differences [15,16]. In addition, ketoprofen does not have a significant effect on the synthesis of proteoglycans by chondrocytes in in vitro and in vivo studies [17], that is, it does not have a negative effect on articular cartilage.

According to our data, when prescribing various forms of Ketonal, the frequency of development of a positive effect was 87% when using the tablet form, 79% when using intramuscular injections and 100% when using Ketonal in the form of 5% cream. Interesting data from JS Walker et al. [18], who showed that in RA patients who “responded” to ketoprofen, before prescribing the drug, there was a significant increase in the concentration of tumor necrosis factor-a and a tendency to an increase in the level of other proinflammatory cytokines compared to patients who “did not respond” to ketoprofen. These data confirm that the pronounced anti-inflammatory and analgesic effects of ketoprofen are associated not only with COX-mediated inhibition of prostaglandin synthesis. The drug provides a rapid and reliable reduction in pain and parameters reflecting the level of inflammation in the joints.

In a clinical endoscopic study of the effectiveness and tolerability of Ketonal in various dosage forms in patients with active rheumatoid arthritis who received Ketonal in the form of suppositories (50 mg each), forte tablets (100 mg each) or retard tablets (150 mg each) for 3 -x months we received confirmation of the high analgesic and anti-inflammatory activity of Ketonal with its good tolerability [19]. The comparative frequency of erosive and ulcerative lesions of the gastrointestinal mucosa when using various NSAIDs is demonstrated in Figure 2. It can be seen that the frequency of damage to the gastrointestinal mucosa with the use of Ketonal is comparable to that with the use of selective COX-2 inhibitors.

Rice. 2. Frequency of damage to the gastrointestinal mucosa due to the use of NSAIDs

Thus,
Ketonal showed high effectiveness in the treatment of joint pain and inflammation in patients with chronic joint diseases in combination with good tolerability.
The drug can be successfully used for long-term treatment of such patients, including elderly patients.
References:
1. Vane JR Inhibition of prostaglandin synthesis as a mechanism of action for the aspiei-like drugs. Nature, 1971; 231; 235–239.

2. Nasonov E.L. Non-steroidal anti-inflammatory drugs (prospects for use in medicine). M., "Anko", 2000, 143 pp.

3. Crofford LJ, Lipsky PE, Brooks P. et.al., Basic biology and clinical application of specific cyclooxygenase–2 inhibitors. Arthr.Rheum., 2000; 43;4–13.

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