Pharmacological properties of the drug Nise gel
Nise gel contains nimesulide, a selective COX-2 inhibitor. It has an analgesic and anti-inflammatory effect due to the inhibition of COX-2, which leads to inhibition of the synthesis of prostaglandins, which are involved in the formation of edema and pain during inflammation. Nimesulide inhibits platelet activation factor, tumor necrosis factor alpha, and the release of proteinases and histamine. Methyl salicylate, a derivative of salicylic acid, has a local irritating and distracting effect. Menthol has an analgesic effect, accompanied by a feeling of cold. The analgesic effect of menthol is associated with stimulation of cold receptors, stabilization of calcium ion flows through the channels of neuronal membranes. Capsaicin has a local irritant effect, causes a local increase in blood flow and tissue hyperemia at the site of application, and promotes the release of endogenous biologically active substances. Nise gel is characterized by high safety of use (virtually no side effects are noted). When applied externally, the gel is gradually absorbed through the skin into the underlying muscle or synovial fluid. Equilibrium concentrations between skin and muscle or synovial fluid are achieved quickly. With local application of Nise gel, systemic absorption is insignificant, since the levels of nimesulide in the blood plasma remained below the detection limit of high-performance liquid chromatography and only after 5 hours very low concentrations (100 μg/l) of hydroxynimesulide in the blood plasma were detected.
Pharmacological group
Nise gel belongs to the group of non-steroidal anti-inflammatory drugs that block the release of substances that provoke pain. In the matter of joint pain, it is necessary to control the synthesis of prostaglandin H2. and E2. At the site of inflammation, these substances are produced with great intensity, and impulses from them enter the spinal cord.
Nise gel is able to block the synthesis of these substances. This action has an analgesic effect. In addition, the use of the gel relieves the severity of inflammation.
If the work of the joints is difficult after sleep, Nise gel is used before the development of the inflammatory process. This allows you to start your day pain-free.
When used topically, nimesulide is not absorbed into the blood or is absorbed in extremely low doses. The maximum possible concentration of the substance is achieved only at the end of the first day of use of the product, and its volume is almost 300 times less than after a single oral dose of nimesulide. No derivative metabolites of the substance are detected in the blood.
Special instructions for the use of the drug Nise gel
The drug is intended for external use. Elderly patients with significant impairment of liver and kidney function, patients with congestive heart failure should use the drug with caution. It is recommended to apply the gel only to intact areas of the skin, avoid contact with open wounds. Do not use the gel under airtight or tight bandages. Avoid getting the gel into the eyes and mucous membranes. Wash your hands thoroughly before and after using the gel. Indications for use of the gel in children and dosage have not been established.
Indications for use of Nise gel
Nise gel is prescribed for diseases of the musculoskeletal system. Among them:
- rheumatoid arthritis;
- joint damage by osteoarthritis;
- radiculitis;
- inflammation of ligaments and articular discs, as well as bursitis;
- muscle pain caused by rheumatism;
- exacerbation of gout.
In addition to diseases, Nise gel is recommended for use after injuries:
- bruises;
- sprains;
- dislocations;
- ligament ruptures.
When the joints are affected due to the progression of psoriasis, you can relieve inflammation by rubbing in Nise gel. However, if there is an ulcer or psoriatic plaque on the surface of the skin above the joint, applying the gel is undesirable, especially when any trauma to the surface of the scaly wound leads to bleeding and increased inflammation.
Nise gel (1% 50g)
INSTRUCTIONS for use of the medicinal product for medical use NIZE®
Registration number: P N012824/02
Trade name: Nise®
International nonproprietary name: nimesulide
Chemical name: N-(4-nitro-2-phenoxyphenyl) methanesulfonanilide
Dosage form: gel for external use
Composition: 1 g of gel contains: active substance: nimesulide 10 mg; excipients: N-methyl-2-pyrrolidone 250 mg, propylene glycol 100 mg, macrogol 315.5 mg, isopropanol 100 mg, purified water 200 mg, carbomer-940 20 mg, butylated hydroxyanisole 0.2 mg, thiomersal 0.1 mg, potassium dihydrogen phosphate 0.2 mg, flavor (Narcissus-938) 4 mg.
Description: transparent gel of light yellow or yellow color, free from foreign particles.
Pharmacotherapeutic group: non-steroidal anti-inflammatory drug (NSAID)
ATX code: M01AX17
Pharmacological action Nise® gel is a new generation non-steroidal anti-inflammatory drug (NSAID) from the sulfonamide class. It has a local analgesic and anti-inflammatory effect. Nimesulide is a selective competitive reversible inhibitor of cyclooxygenase type II (endoperoxide-prostaglandin-H2 synthetase). Reduces the concentration of short-lived prostaglandin H2, a substrate for kinin-stimulated synthesis of prostaglandin E2, at the site of inflammation and in the ascending pathways of pain impulses in the spinal cord. A decrease in the concentration of prostaglandin E2 (a mediator of inflammation and pain) reduces the activation of EP type prostanoid receptors, which is manifested by analgesic and anti-inflammatory effects. When applied topically, it causes a weakening or disappearance of pain at the site of application of the gel, including pain in the joints at rest and during movement, reduces morning stiffness and swelling of the joints. Helps increase range of motion.
Pharmacokinetics When applying the gel, the concentration of the active substance in the systemic circulation is extremely low. The maximum concentration after a single application is observed at the end of the first day; its value is more than 300 times lower than that for oral dosage forms of nimesulide. No traces of the main metabolite of nimesulide, 4-hydroxynimesulide, are found in the blood.
Indications Local symptomatic treatment of inflammatory and degenerative diseases of the musculoskeletal system (articular syndrome with exacerbation of gout, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, osteochondrosis with radicular syndrome, radiculitis, inflammatory damage to ligaments, tendons, bursitis, sciatica, lumbago). Muscle pain of rheumatic and non-rheumatic origin. Post-traumatic inflammation of soft tissues and the musculoskeletal system (damage and rupture of ligaments, bruises).
Contraindications Hypersensitivity to nimesulide and the components of the drug; erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, bleeding from the gastrointestinal tract, dermatoses, damage to the epidermis and skin infections in the area of application; severe renal (creatinine clearance less than 30 ml/min.) or liver failure, a history of bronchospasm associated with the use of acetylsalicylic acid or other NSAIDs, pregnancy and lactation, children under 7 years of age.
With caution : Liver failure; renal failure; severe heart failure; arterial hypertension; diabetes mellitus type 2; elderly and children's age.
Directions for use and dosage : Externally. Before applying the gel, wash and dry the skin surface. Apply a uniform thin layer of gel approximately 3 cm long to the area of maximum pain, without rubbing, 3-4 times a day. The amount of gel and the frequency of its use (no more than 4 times a day) may vary depending on the size of the treated area and the patient’s response. Do not use the gel for more than 10 days without consulting a doctor.
Side effects Local reactions: itching, urticaria, peeling, transient change in skin color (not requiring discontinuation of the drug). If any adverse reactions occur, you should stop using the drug and consult your doctor. When applying the gel to large areas of the skin or with prolonged use, the development of systemic adverse reactions is possible: heartburn, nausea, vomiting, diarrhea, gastralgia, ulceration of the gastrointestinal mucosa, increased activity of “liver” transaminases; headache, dizziness; fluid retention, hematuria; allergic reactions (anaphylactic shock, skin rash); thrombocytopenia, leukopenia, anemia, agranulocytosis, prolongation of bleeding time.
Overdose Cases of drug overdose have not been described. However, when large quantities of gel (exceeding 50 g) are applied to large areas of skin, the development of an overdose cannot be ruled out. There is no specific antidote. You need to see a doctor.
Interaction with other drugs Pharmacokinetic interaction with drugs that compete for association with blood plasma proteins is not excluded. Caution should be exercised when using Nise® simultaneously with digoxin, phenytoin, lithium preparations, diuretics, cyclosporine, methotrexate, other NSAIDs, antihypertensive and antidiabetic agents. Before using the gel, you should consult your doctor if you are using these products or are under medical supervision.
Special instructions The drug is recommended to be applied only to intact areas of the skin, avoiding contact with open wounds. Avoid getting the gel into the eyes and other mucous membranes. Do not use the gel under airtight dressings. After applying the gel, wash your hands with soap. Close the tube tightly after using the gel.
Release form Gel for external use 1%. 20 g or 50 g in a laminated aluminum tube equipped with a membrane to control the first opening. The tube is packed in a cardboard box with instructions for use.
Shelf life: 2 years. Do not use the drug after the expiration date indicated on the package.
Storage conditions List B. In a dry place, protected from light, at a temperature not exceeding 25 °C. Do not freeze. Keep out of the reach of children!
Conditions for dispensing from pharmacies Without a prescription.
Manufacturer Dr. Reddy's Laboratories Ltd., Hyderabad, Andhra Pradesh, India
Manufacturing address Dr. Reddy's Laboratories Ltd. Plot No. 41, Nasigere Village, Kasaba Hobli, KIADB, Malur-563130, Karnataka, India.
Send consumer complaints to the following address: Representative office: 115035, Moscow, Ovchinnikovskaya embankment, 20, building 1 tel., 783-29-01 fax
Efficacy of Nise gel (nimesulide) as an additive therapy in patients with rheumatoid arthritis
The main indicator for prescribing NSAIDs is pain, which in rheumatoid arthritis (RA) is caused by complex processes characteristic of immune-mediated inflammation. Inflammation and pain are initiated by various algogens that excite peripheral nociceptor receptors, which are abundantly supplied to all joint tissues. Two types of nerve fibers take part in the transmission of pain: fast myelinated A-delta fibers are interested in conducting acute localized pain, and non-myelinated C-fibers carry out poorly localized pain. Having reached the reticular formation and thalamus through the spinal cord, pain impulses spread to parts of the brain, which can form a “pathological” focus of pain [2]. The main directions of pharmacological pain relief are: firstly, reducing or eliminating the activation of peripheral nociceptors, secondly, influencing the synaptic transmission of pain stimuli and, thirdly, increasing the influence of the antinociceptive system on the transmission of the pain signal. Systemic administration of NSAIDs helps block peripheral nociceptors and impulse transmission to the central nervous system. The anti-inflammatory and analgesic effect of this group of drugs is due to the inhibitory effect on the enzyme cyclooxygenase (COX), mainly its anti-inflammatory isoform COX-2. The expression of COX-2 is especially high in the synovium of patients with RA [3]. While they have similar analgesic effects, NSAIDs differ in toxicity. Those with a greater inhibitory effect on COX-1 are more likely to cause side effects. COX-2 inhibitors with a short half-life are safer. When choosing a drug, it is necessary to take into account the speed of effect and safety of the drug. The latter is especially important in elderly people, taking into account the peculiarities of drug metabolism, as well as the compatibility of NSAIDs with antihypertensive, hypoglycemic and other drugs for the treatment of comorbid diseases. Selective COX-2 inhibitors are safer. But many doctors believe that their effectiveness is less than that of “classical” NSAIDs, which includes diclofenac, recognized as the “gold” standard for analgesic effect [4]. In a comparative study, diclofenac at therapeutic doses had a more pronounced inhibition of COX-2 activity than celecoxib, refecoxib, meloxicam, ibuprofen, and naproxen. Diclofenac has less effect on COX-1. It is the balance of the effect that ensures its high efficiency [5]. Nimesulide is the first NSAID with selective inhibition of COX-2, which has the shortest half-life (1.8–4.7 hours). The drug is widely used in the treatment of various inflammatory diseases, having an advantage for patients with “aspirin” asthma. A comparison of the effectiveness and safety of nimesulide and diclofenac in a double-blind study involving 122 patients with glenohumeral periarthritis showed that after 14 days the researchers assessed the effect as “good/very good” in 79% of patients receiving nimesulide and 78% receiving diclofenac. 5 and 13 patients dropped out of the study, respectively [6]. Drugs that “save” COX-1, such as meloxicam and nimesulides, are safer in this regard, but are also not without side effects on the gastrointestinal tract and other organs. To eliminate the side effects of NSAIDs, it is recommended to use NSAIDs for local use as additive therapy - ointments, gels, creams that create a high concentration of the active substance in the periarticular tissues and practically do not enter the bloodstream during such use [7]. The use of local forms of NSAIDs is especially important in elderly people who have several risk factors for the development of side effects. In the literature, the issue of the severity of the analgesic effect of “classical” NSAIDs and those selective for COX-2 is still being debated, which served as the basis for conducting an open comparative study of diclofenac gel and nimesulide gel (Nise) (Dr. Reddy's Lab) in RA. The purpose of the study was to compare the clinical effect of two local forms of NSAIDs - diclofenac and nimesulide, as well as the speed of onset of the analgesic effect and its duration. Treatment regimen: for 14 days, the patient applies a 4-5 cm strip of gel three times a day to the skin of the most affected knee joint and rubs it in a circular motion into the skin over the entire surface of the joint. Inclusion criteria were: • a reliable diagnosis of RA according to the ACR criteria • the presence of knee arthritis and pain 40 mm VAS • age over 18 and under 75 years • outpatient treatment • written consent of the patient to participate in the study • approval of the local ethics committee for the study • the last intra-articular injection of corticosteroids should be no earlier than 3 months. before inclusion in the study • therapy with other drugs or agents that have an analgesic effect is excluded • the dose of “basic” and corticosteroid drugs should remain stable, the dose of NSAIDs can be reduced during the study period with a note in the individual chart. Patients with active comorbid infection, severe organ failure, and damage or infection of the skin over the knee (studied) joint were not included. Materials and methods of research The study included 60 patients with RA, of which 30 received local therapy with Nise gel, the other 30 - diclofenac gel. The general characteristics of the patients are presented in Table 1. To determine the effectiveness of local therapy, we used a pain VAS, which assessed pain in the most affected joint at rest, during movement, while standing/sitting, and going down/ascending stairs. Functional abilities were assessed using a total score from 0 to 4 for the ability to wash, dress, and go down/ascend stairs. Arthrosonography of the knee joints was performed on a Sono-Diagnost 360 device from Philips, with a linear sensor with a power of 7.5 MHz, in real time according to the following parameters: the presence of fluid in the knee joint and Baker's cysts, the thickness of the synovial membrane. Statistical processing of the obtained data was carried out using the Statistica program, version 5, using descriptive statistics methods, Wilcoxon criterion, l - square (PhD O.V. Stepanets). Study results All patients completed the full two-week course of treatment. The analgesic effect of the compared gel forms of NSAIDs was comparable. The severity of pain in the knee joint under study significantly decreased both when walking on level ground and when going up/down stairs in both groups, which is presented in Table 2. It should be noted that the patients were on an outpatient basis, that is, without restrictions on the motor mode. The speed of onset of the effect was different, on average it was 30 minutes, the duration of analgesia lasted from 4 to 6 hours, which indicates the need to apply the gel three times to the affected joint during the day. Despite the fact that with local cutaneous therapy, very little active substance enters the joint cavity, according to sonography of the joint, a decrease in effusion, the size of Baker's cysts and the thickness of the synovial membrane was noted, which indicates an anti-inflammatory effect of the studied local forms, although weakly expressed. In group 1, the number of patients with positive results was slightly greater than in group 2 (Table 3). We assessed the functional ability of patients using 17 parameters, in which 0 points meant that the manipulations were carried out without difficulty, and the most difficult ones were assessed as 4 points. Reducing the severity of pain had a positive effect on the ability to perform ordinary daily manipulations (movement, dressing, toileting, performing light and heavy work) in 60% of patients 1 gr. and 66% – 2 gr. Table 4 shows the individual dynamics of the functional activity of patients in percentage terms, showing that more than half of the patients showed an improvement of 20–30%, which is considered significant according to ACR criteria. The general assessment of health status, which was assessed by the patient using VAS, showed significant differences before and after treatment. In group 1, the indicators improved from 64.1±19.7 to 51.8±19.1(p<0.005), in group 2 – from 53.57±17.3 to 41.22±16.9 (p <0.005). The effect of local therapy was assessed as good by 37.9% of patients in group 1 and 33.3% in group 2, and as satisfactory by 48.3 and 50%, respectively. Three patients who received Nise and five who received diclofenac did not notice any effect. During therapy, in 4 patients of group I, it was possible to reduce the dose of oral Nise by 100 mg. The gel forms were well tolerated; no adverse reactions (local or systemic) were noted. Conclusion The study confirmed the possibility of enhancing the analgesic effect of complex therapy for RA by including local gel forms of NSAIDs. In terms of analgesic effect, Nise gel is not inferior to the “classic” NSAID - diclofenac and can be used as an additive agent to enhance the analgesic effect in patients with RA and even allows for a dose reduction when taking NSAIDs systemically. In addition, the drug Nise gel has a good anti-inflammatory effect. Local therapy with Nise gel is safe with regard to the development of adverse events. We did not notice an increase in blood pressure in patients suffering from arterial hypertension, and there were no patients with the development of gastralgia.
Literature 1. National guide “Rheumatology”, 2008, p. 197 2. Kukushkin M.L., Khitrov N.K. General pathology of pain, M., 2004, 20–42 3. Siegle I, Klein T., Backman YT ea Expression of cyclooxygenase-1 and cyclooxygenase-2 in human synovial tissue. 4. Mr Cormack K., Twycross R. Are COX–2 selective inhibitors effective analgesics? Pain Reviews, 2001, v 8, no. 1, 15–26 5. Van Hecken A., Schwarty YI, Depre M ea Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen and naproxen on COX–2 versus COX–1 in healthy volunteers. J. Clin. Pharmac., 2000, 40(10), 1109–20. 6. Goryachev D.V., Balabanova R.M. Nimesulide – the beginning of the era of selective COX-2 inhibitors Russian Medical Journal. – 2003. – vol. 11 – No. 25. – p. 1331–1333. 7. Moore RA, Tramer MR, Carall D. Quantative systematic review of topically applied NSAIDs Brit. Med. J., 1998, 316, 333–338