KETONAL cream 30g

Nosological classification (ICD-10)

M02.3 Reiter's disease
M06.9 Rheumatoid arthritis, unspecified
M07.3 Other psoriatic arthropathies (L40.5+)
M19.9 Arthrosis, unspecified
M45 Ankylosing spondylitis
M54 Dorsalgia
M54.1 Radiculopathy
M71 Other bursopathies
M77.9 Enthesopathy, unspecified
M79.1 Myalgia
M79.2 Neuralgia and neuritis, unspecified
T14 Injury of unspecified location
T14.3 Dislocation, sprain and damage to the capsular-ligamentous apparatus of a joint of an unspecified area of the body
T14.9 Injury, unspecified

Indications for the drug Ketonal®

Symptomatic treatment of painful and inflammatory processes of various origins, including:

rheumatoid arthritis and periarthritis;

ankylosing spondylitis (Bechterew's disease), psoriatic arthritis, reactive arthritis (Reiter's syndrome);

osteoarthritis of various localizations;

tendonitis, bursitis, myalgia, neuralgia, radiculitis;

injuries of the musculoskeletal system (including sports), bruises of muscles and ligaments, sprained ligaments, rupture of ligaments and muscle tendons.

Contraindications

hypersensitivity to ketoprofen or other components of the drug, as well as salicylates, tiaprofenic acid or other NSAIDs, fenofibrate, UV blockers, fragrances;

a history of attacks of bronchial asthma after the use of NSAIDs and salicylates;

pregnancy (III trimester);

children's age (up to 15 years);

violation of the integrity of the skin (eczema, weeping dermatitis, open or infected wound);

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 with the drug.

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

Special instructions for the use of the drug Ketonal cream, gel

If a skin rash appears, topical use of the drug should be discontinued. 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.

Side effects

The most common manifestations associated with the use of a cream containing ketoprofen are local manifestations.

Classification of adverse reactions according to the frequency of their detection: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000).

Allergic reactions: very rarely - angioedema, anaphylaxis.

From the skin and skin appendages: 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.

Instructions for use KETONAL® (KETONAL)

The simultaneous use of Ketonal with NSAIDs, including selective COX-2 inhibitors, should be avoided.

Undesirable effects can be minimized by prescribing the drug at the minimum dose for the shortest period of time necessary to control symptoms.

Elderly patients have an increased incidence of side effects of NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

Gastrointestinal bleeding, ulceration or perforation with risk of death has been reported for all NSAIDs at any stage of treatment, with or without warning symptoms or a history of previous severe gastrointestinal illness.

Some epidemiological data suggest that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity compared with some other NSAIDs, especially at high doses.

In patients with a history of peptic ulcer disease, especially those complicated by bleeding or perforation, and in elderly patients, the risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs. In such patients, treatment should be started with the minimum effective dose.

For these patients, as well as for patients who require concomitant use of low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, concomitant administration of drugs that protect the gastrointestinal mucosa (for example, misoprostol or proton pump blockers) may be required.

Patients who have experienced gastrointestinal toxicity, especially elderly patients during the initial stages of treatment, should report any unusual abdominal symptoms. The risk of gastrointestinal bleeding should be kept in mind.

Caution is required when using the drug in patients receiving concomitant therapy with drugs that may increase the risk of ulcerative lesions or bleeding, for example, ingestion of corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid.

If gastrointestinal bleeding or ulceration develops in patients receiving ketoprofen, treatment should be discontinued.

NSAIDs should be prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), because their aggravation is possible.

Cardiovascular and cerebrovascular effects:

Appropriate monitoring and consultation are required for patients with a history of hypertension and/or mild to moderate congestive heart failure, manifested by fluid retention or edema, associated with NSAID treatment.

Clinical experience and epidemiological data suggest that the use of some NSAIDs (especially at high doses and during long-term treatment) may be associated with an increased risk of arterial thrombosis (eg, myocardial infarction or stroke). There is insufficient data to exclude such a risk for ketoprofen.

In patients with uncontrolled hypertension, congestive heart failure, known coronary artery disease, peripheral arterial disease and/or cerebrovascular disease, treatment with ketoprofen should be undertaken only after careful assessment of the appropriateness of its use. Such an analysis should be done before starting long-term treatment in patients with risk factors for cardiovascular disease (for example, hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients suffering from bronchial asthma, in combination with chronic rhinitis, chronic sinusitis and/or nasal polyposis, are more likely to experience allergic reactions after taking acetylsalicylic acid and/or NSAIDs than in the general population. Administration of this product may cause an attack of bronchial asthma.

Caution is also required in patients with hemostasis disorders, hemophilia, von Willebrand disease, severe thrombocytopenia and renal or liver failure, as well as in those taking anticoagulants (coumarin and heparin derivatives, low molecular weight heparins).

In patients with liver damage receiving diuretics, after major surgical interventions with developed hypovolemia, and especially in elderly patients, urine output and renal function should be carefully monitored.

Ketoprofen should be prescribed with caution to patients with chronic alcoholism.

Severe skin reactions (some of them fatal) such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed extremely rarely in association with the use of NSAIDs. Patients are at greatest risk of developing these reactions at the beginning of treatment; in most cases, the occurrence of a reaction is noted within the first month of treatment. Ketonal® should be discontinued at the first appearance of a skin rash, changes in the mucous membranes or other signs of hypersensitivity.

As with any long-term treatment with non-steroidal antirheumatic drugs, therapy with ketoprofen requires monitoring of blood cells, as well as liver and kidney function, especially in elderly patients. When CC < 20 ml/min, dose adjustment of ketoprofen is necessary.

Like other NSAIDs, ketoprofen mask the signs and symptoms of infectious diseases.

Ketonal® should be discontinued before major surgery.

Ketonal® capsules 50 mg and Ketonal® forte contain lactose. Therefore, the drug should not be prescribed to patients with rare hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose or galactose.

Ketonal® injection solution contains 12.3 vol% ethanol. Every 2 ml dose contains 0.2 g of ethanol. This may have a negative effect on patients with alcoholism, those with brain damage or disease, or pregnant or breastfeeding women.

Impact on the ability to drive vehicles and operate machinery

Patients should be warned about the possible occurrence of drowsiness, dizziness, or convulsions while taking the drug. If there is a risk of developing such reactions, patients should refrain from driving vehicles and operating machinery.

Results of preclinical safety studies

Acute toxicity. After oral administration, the LD50 of ketoprofen was 360 mg/kg in mice, 160 mg/kg in rats, and 1300 mg/kg in guinea pigs. The LD50 of ketoprofen is several times higher than that of indomethacin.

Chronic toxicity. Ketoprofen was administered orally to rats for 4 weeks at doses of 2, 6 or 18 mg/kg. 10% of animals receiving ketoprofen at a dose of 18 mg/kg died on days 6-30, some had ulceration of the intestinal mucosa. In dogs receiving the same dose, only intestinal ulcerations were described, while no animals died. Among the animals receiving indomethacin at a dose of 6 mg/kg body weight, half died; all animals receiving 18 mg/kg body weight died.

In a 6-month study, rats were administered orally ketoprofen at doses of 3, 6 or 9 mg/kg. After 8 weeks, 53% of male rats treated with 6 mg/kg and 67% of male and 20% of female rats treated with 9 mg/kg died. In animals receiving 9 mg/kg, plasma concentrations of all proteins decreased and spleen weight increased. and liver. Histopathological studies of tissues from surviving animals did not reveal significant pathological changes.

Carcinogenicity, mutagenicity and effects on fertility. Long-term toxicity studies in mice administered orally ketoprofen up to 32 mg/kg/day did not reveal carcinogenic effects of this drug. The Ames test did not show any mutagenic properties. Ketoprofen did not affect the fertility of male rats that received up to 9 mg/kg/day orally. In female rats receiving 6 or 9 mg/kg/day, the number of implantations was reduced. In male rats and dogs, suppression of spermatogenesis was found. Dogs and male monkeys treated with high doses of ketoprofen experienced a decrease in testicular weight.

Teratogenicity. Neither teratogenic effects nor effects on the fetus were shown in mice receiving ketoprofen up to 12 mg/kg/day and in rats receiving up to 9 mg/kg/day. In rabbits, doses of ketoprofen toxic to the maternal organism were embryotoxic, but had a teratogenic effect.

special instructions

Avoid contact of the cream with mucous membranes and eyes. If any side effects occur, you should stop using the drug and consult a doctor.

If the patient forgets to apply the cream, it should be applied at the time the next dose is due, but not double it.

Cream for external use Ketonal® can be used in combination with other dosage forms of Ketonal® (capsules, tablets, suppositories). The total daily dose, regardless of the dosage form, should not exceed 200 mg.

If skin reactions occur, incl. developed during combined use with octocrylene-containing drugs, treatment should be stopped immediately. To reduce the risk of developing photosensitivity, it is recommended to protect the areas of skin treated with the cream with clothing from exposure to UV radiation throughout the entire treatment period and for another 2 weeks after stopping use. Do not use as occlusive dressings.

You should wash your hands thoroughly after each application of the drug.

Effect on ability to concentrate. There is no data on the effect of Ketonal® cream on psychophysical activity.

Ketonal DUO in the treatment of pain syndrome

Pain is the most common symptom of a wide variety of diseases. The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensation and emotional experience associated with actual or potential tissue damage or described in terms of such damage [1]. Pain is heterogeneous, has many characteristics and occurs due to various pathophysiological mechanisms underlying a particular disease. That is why, for successful treatment of pain syndrome, drug therapy should be selected in accordance with the type of pain and the characteristics of its pathogenesis.

Classifications of pain syndrome

In medical practice, acute and chronic pain are distinguished. Acute pain is caused by tissue damage and decreases as it heals, is characterized by a sudden onset, short duration, clear localization and, as a rule, is a symptom of some disease. Acute pain performs a signaling function, warning of danger and ensuring the mobilization of the body's defenses aimed at eliminating the damaging factor. Pain is called chronic if it persists after the healing process is complete. There is still no consensus on the time criterion for pain chronicization, that is, it is unclear at what point in time chronicization occurs. According to the International Association for the Study of Pain, pain is considered chronic if it lasts at least 3 months, and in accordance with the criteria of DSM-IV (Diagnostic and Statistical Manual of mental disorders) - at least 6 months. In any case, chronic pain is not accompanied by signs characteristic of acute pain, does not have a protective function and becomes the cause of suffering for the patient. However, the main difference between chronic pain and acute pain is not the time factor, but qualitatively different neurophysiological, psychophysiological and clinical relationships. According to the generally accepted pathophysiological classification, pain is divided into nociceptive, neuropathic and dysfunctional.

Nociceptive pain

occurs when peripheral pain receptors - “nociceptors”, are irritated, localized in almost all organs and systems (coronary syndrome, pleurisy, pancreatitis, gastric ulcer, renal colic, articular syndrome, damage to the skin, ligaments, muscles, etc.) due to damage and /or inflammation of soft tissues. With this type of pain, the factor that caused it is usually obvious, the pain is well localized (nociceptive pain is usually localized in the area of damage). When describing nociceptive pain, patients most often use the terms “squeezing”, “aching”, “pulsating”, “cutting”. In the treatment of nociceptive pain, a good therapeutic effect can be obtained by prescribing simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs). When the cause is eliminated (cessation of irritation of the “nociceptors”), nociceptive pain goes away [2].

Neuropathic pain

occurs due to damage to various parts (peripheral and central) of the somatosensory nervous system [2]. The causes of neuropathic pain can be damage to the afferent somatosensory system at any level, from peripheral sensory nerves to the cerebral cortex, as well as disturbances in descending antinociceptive systems. This type of pain occurs in diabetic polyneuropathy, postherpetic and trigeminal neuralgia, post-stroke condition, and phantom pain. The general characteristics of neuropathic pain are: duration, persistent nature, variety of sensory manifestations (hypersthesia, hyperpathia, allodynia, loss of various types of sensitivity), combination with autonomic disorders (hyperemia or decreased blood flow, hyper- or anhidrosis in the pain area) and motor disorders. Standard analgesics and NSAIDs are ineffective in the treatment of neuropathic pain [3].

As a rule, in most cases (radiculopathy, carpal tunnel syndrome, cancer, complex regional pain syndrome), pain is of a mixed nature, including both nociceptive and neuropathic components [2]. In the treatment of mixed pain, various therapeutic approaches are used. The peculiarity of dysfunctional pain is that the examination fails to identify the cause of the pain or organic diseases that could explain the origin of the pain. Among the main reasons contributing to the development of this type of pain are not organic pathology, but psychological and social factors. Typical examples of dysfunctional pain are fibromyalgia, tension headaches, and psychogenic pain (somatoform disorders) [4]. Another characteristic of the pain syndrome that influences the choice of analgesic therapy is its intensity. It is generally accepted to divide pain into mild, moderate and severe.

Pain therapy

Currently, non-steroidal anti-inflammatory drugs occupy a leading position in the treatment of pain syndrome. Due to their mechanism of action, NSAIDs have proven themselves to be best for acute nociceptive pain of mild to moderate intensity. The advantage of NSAIDs is that they have not only an analgesic but also an anti-inflammatory effect. The therapeutic effects of NSAIDs are based on reducing the synthesis of prostaglandins from arachidonic acid through inhibition of the enzyme cyclooxygenase (COX). There are two isoforms of COX: COX-1 is constantly present in all tissues, COX-2 is synthesized against the background of inflammation. Of particular interest are new dosage forms of NSAIDs that make it possible to maintain a pronounced anti-inflammatory and analgesic effect and at the same time reduce the degree of undesirable effects on the gastrointestinal tract [5–7].

Ketonal DUO: advantages of the new form

New NSAIDs include Ketonal (Lek, Slovenia), the main active ingredient of which is ketoprofen. According to its chemical structure, ketoprofen belongs to the group of propionic acid derivatives. It non-selectively inhibits the enzymes COX-1 and COX-2 and, partially, lipoxygenase. The powerful anti-inflammatory and analgesic effect of ketoprofen is due to the fact that it has both a peripheral and central mechanism of action, therefore it is used even in cases of severe pain. In peripheral tissues, ketoprofen suppresses the synthesis of prostaglandins, stabilizes lysosomal membranes, and has distinct anti-bradykinin activity. Due to its high lipophilicity, the ketoprofen molecule penetrates the blood-brain barrier, where it realizes its central effect: it reduces the synthesis of prostaglandins and blocks excitatory amino acid receptors in the spinal cord. Ketonal DUO is an innovative form of NSAID. It differs from both regular and extended-release forms in the way it releases the active substance. Modified release capsules contain two types of pellets: white (about 60% of the total) and yellow coated pellets (about 40%). Ketoprofen is quickly released from white pellets and slowly from yellow ones, which determines the combination of rapid and prolonged action of the drug [8]. One capsule of Ketonal DUO contains 150 mg of ketoprofen, which does not exceed the standard daily dose of the drug. Ketonal DUO modified release capsules have the following advantages:

contain the optimal daily dose of ketoprofen, which allows you to reduce the frequency of taking the drug to once a day, which is convenient to use;
provide a more stable concentration of the drug in the blood over a 24-hour interval;
minimize the irritating effect of the drug on the gastrointestinal tract;
increase patient compliance due to a single daily dose of the drug.

Ketonal DUO: proven effectiveness

Currently, extensive experience has been accumulated in the use of ketoprofen in various clinical situations. A double-blind, placebo-controlled study conducted by R. Lange, R. Lentz (1995) in parallel groups in 345 patients showed the advantage of ketoprofen for the relief of acute pain over drugs such as naproxen and ibuprofen [9]. Ketoprofen is successfully used for “low back pain” syndrome. In a randomized, double-blind, multicenter study by H. Zippel, A. Wagenitz (2007) involving 370 patients, ketoprofen at a dose of 50 mg 2 times a day intramuscularly was more effective than diclofenac at a dose of 75 mg 2 times a day intramuscularly. Patients receiving ketoprofen showed a more pronounced reduction in pain with good tolerability [10]. B.R. Gelfand et al. (2002) compared the analgesic effectiveness of ketoprofen and ketorolac in patients in the postoperative period. The results of the study showed that the severity of pain on the visual analogue scale was significantly lower in the group receiving ketoprofen compared to the group of patients taking ketorolac. Adverse events were observed in 4% of patients taking ketoprofen and in 14% of patients taking ketorolac. No serious adverse events were observed in patients receiving ketoprofen as analgesic therapy [11].

Ketoprofen is widely used abroad for analgesia in the postoperative period. In the work of F. Aubrun et al. (2000) showed that the administration of ketoprofen leads to a reduction in the dose of morphine in the postoperative period by 33% [12]. Ketoprofen has pronounced anti-inflammatory and analgesic effectiveness in the treatment of rheumatic diseases. Ketoprofen shows an effectiveness that exceeds that of diclofenac, with better tolerability. In a study by I. Jokhio (1998), with a good analgesic effect in 87% of patients taking ketoprofen, good tolerability was noted in 72%, while among patients taking diclofenac, good tolerability was observed in only 50% of cases [13]. A. Calin et al. (1977) found that ketoprofen at a dose of 150–300 mg per day for 3 months also showed better efficacy and tolerability compared with ibuprofen at a daily dose of 1200–2400 mg in patients with rheumatoid arthritis in a double-blind, controlled study in parallel groups [14 ].

In Russia, in 2012, a multicenter (including 10 cities of the Russian Federation) open study was conducted to evaluate the effectiveness and safety of the use of the drug Ketonal DUO in the treatment of dorsalgia. A total of 349 patients took part in the study and received Ketonal DUO at a dose of 150 mg/day for 7 days. The data obtained demonstrated a significant reduction in the level of back pain both at rest and during movement (p

Conclusion

Thus, the powerful analgesic and anti-inflammatory effect of the drug Ketonal DUO, as well as proven good tolerability, combined with the convenience of a single dose, allow us to recommend the drug for use in the treatment of a wide range of pain syndromes.