Naklofen injection solution 75 mg/3 ml in 3 ml ampoules in blister No. 5x1

Pharmacological properties of the drug Naklofen

Diclofenac ([o-(2,6 dichloroanilino)phenyl]acetate sodium salt) is an NSAID with pronounced anti-inflammatory, analgesic and antipyretic effects. The mechanism of action is associated with the inhibition of COX and the resulting disruption of prostaglandin synthesis. By blocking the synthesis of prostaglandins, diclofenac eliminates or significantly reduces the severity of symptoms of inflammation. Diclofenac reduces prostaglandin-induced increased sensitivity of nerve endings to mechanical stimuli and biologically active substances that are formed at the site of inflammation. Helps lower body temperature, preventing the effect of prostaglandins on the hypothalamic region of the thermoregulation process, reduces the concentration of prostaglandins in menstrual blood and the intensity of pain during primary dysmenorrhea. During treatment with diclofenac, the concentration of prostaglandins in the urine, gastric mucosa and synovial fluid decreases. During the treatment of rheumatoid arthritis, the drug intensively penetrates into the joint cavity, reduces pain at rest and during movement, helps to increase the range of motion in the affected joints, and reduces morning stiffness and swelling of the joints. Naklofen is used to treat rheumatic diseases; to eliminate pain of any localization of various origins. The tablets are coated with an acid-resistant coating and dissolve after entering the intestines. Naklofen Duo contains diclofenac in the form of granules that are resistant to the action of gastric juice and prolonged-release granules, as a result of which the capsules have both rapid and prolonged action. Retard tablets are intended for long-term treatment. After oral administration, diclofenac sodium is rapidly absorbed in the duodenum and small intestine. Over 90% of the drug is absorbed, but due to metabolism during the initial passage through the liver, bioavailability is about 60%. About 99% of diclofenac binds to plasma proteins, mainly albumin. The half-life is 1–2 hours. More than 70% of diclofenac is excreted in the urine in the form of biologically inactive metabolites, only 1% is excreted unchanged. Diclofenac easily penetrates into the synovial fluid, where its concentration reaches 60–70% of the level in the blood serum. After 3–6 hours, the concentration of the drug and its metabolites in the synovial fluid is higher than in the blood serum. Diclofenac is eliminated from synovial fluid much more slowly than from blood serum.

Naklofen injection solution 75 mg/3 ml in 3 ml ampoules in blister No. 5x1

Name

Naklofen solution din. 75mg3ml per amp. 3ml per blister. in pack №5x1

Description

A clear, colorless or light yellow solution, practically free of particles.

Main active ingredient

Release form

The solution for intramuscular administration is transparent, colorless or slightly yellowish, without visible mechanical inclusions.

Dosage

75mg 3ml

special instructions

The drug, when administered intramuscularly, is intended for the treatment of:

• inflammatory and degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, arthrosis, spondyloarthritis, vertebral pain syndrome, extra-articular rheumatism;
• acute attacks of gout;
• renal and hepatic colic;
• inflammation, pain and swelling after injuries and operations;
• severe migraine attacks.

The drug, when administered as an intravenous infusion, is intended for the treatment or prevention of postoperative pain.

Pharmacodynamics

Diclofenac is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. It inhibits the activity of cyclooxygenase and therefore the synthesis of prostaglandins. During treatment with diclofenac, a decrease in prostaglandin levels is observed in urine, gastric mucus and synovial fluid. The drug is used to treat all forms of rheumatic diseases, as well as to reduce pain of various origins.

Pharmacokinetics

Distribution. Maximum plasma concentration is achieved after half an hour. More than 99% of diclofenac is bound to plasma proteins, mainly albumin. Diclofenac enters the synovial fluid, where it reaches a concentration of 60 to 70% of the plasma value. After a period of time from 3 to 6 hours, the concentration of the active substance and its metabolites in the synovial fluid is higher than in plasma. Diclofenac is eliminated more slowly from synovial fluid than from plasma. Metabolism and excretion. The biological half-life (T1/2) is 1? 2 hours. With mild renal or hepatic dysfunction, it remains unchanged. Diclofenac is almost completely metabolized in the liver, mainly by hydroxylation and methoxylation. About 70% of the drug dose is excreted in the urine in the form of pharmacologically inactive metabolites. Only 1% of diclofenac is excreted unchanged. The remainder of the metabolites are excreted in bile and feces. In elderly patients, absorption, metabolism or excretion of the drug is not significantly altered.

Directions for use and doses

Side effects can be minimized by using the minimum effective dose for the minimum period necessary to control symptoms (see Precautions section). Naklofen injection solution can be administered intramuscularly, by deep injection into the upper outer quadrate of the gluteus maximus muscle, or as a slow intravenous infusion after dilution, as described in the instructions. Naklofen injection solution (for intramuscular or intravenous administration) should not be used for more than two days; If necessary, treatment can be continued with Naklofen tablets, capsules or suppositories. Each ampoule is intended for single use only. The solution should be used immediately after opening the ampoule. Any unused contents must be discarded. Intramuscular injection In order to prevent damage to nerves or other tissues at the site of intramuscular injection, the following rules must be observed. The dose is usually one 75 mg ampoule per day, by deep injection into the superior outer quadrant of the gluteus maximus muscle. If two injections per day are required, then one injection is given in each buttock. Alternatively, one 75 mg ampoule can be combined with other dosage forms of Naklofen (enteric-coated tablets, extended-release tablets, capsules or suppositories) up to a maximum daily dose of 150 mg. For migraine attacks, available clinical experience is limited to use as follows: treatment begins as early as possible with 1 ampoule of 75 mg, if necessary, treatment is continued with suppositories on the same day at a dose of up to 100 mg. The total dose on the first day should not exceed 175 mg. There is no data on the use of Naklofen for more than 1 day for migraine. If it is necessary to continue treatment in subsequent days, you should limit yourself to the use of suppositories in a daily dose of up to 150 mg, divided into several single doses. Intravenous infusions Naklofen solution for injection should not be administered as an intravenous bolus injection. Immediately before starting the intravenous infusion, Naklofen, depending on the required duration, should be diluted in 100? 150 ml of 0.9% sodium chloride solution or 5% glucose solution, buffered sodium bicarbonate injection (0.5 ml of 8.4% solution or 1 ml of 4.2%) taken from a freshly opened container; add to this solution the contents of one ampoule of Naklofen. Only clear solutions can be used. If the solution contains crystals or sediment, it cannot be used for infusion. Two alternative dosage regimens for Naklofen, injection solution are recommended. For the treatment of moderate to severe postoperative pain, 75 mg should be administered continuously over 30 minutes to 2 hours. If necessary, treatment can be repeated after a few hours, but the dose should not exceed 150 mg in any 24-hour period. To prevent postoperative pain, a loading dose of 25-50 mg should be administered 15 minutes to 1 hour after surgery, followed by a continuous infusion of approximately 5 mg/hour up to a maximum daily dose of 150 mg. Selected patient groups Elderly patients (65 years and older) The use of the minimum effective dose is recommended. Patients with proven congestive heart failure (NYHA II-IV), coronary artery disease, peripheral arterial disease and/or cerebrovascular disease Diclofenac is contraindicated in patients with proven congestive heart failure (NYHA II-IV), coronary artery disease, peripheral arterial disease and/or cerebral vessels. Patients with impaired renal function Diclofenac is contraindicated in patients with severe renal impairment. Since specific studies have not been conducted in patients with impaired renal function, specific recommendations for dose adjustment cannot be made. Caution is recommended when using diclofenac in patients with mild to moderate renal impairment. Patients with impaired liver function Diclofenac is contraindicated in patients with severe hepatic impairment. Since specific studies have not been conducted in patients with impaired liver function, specific recommendations for dose adjustment cannot be given. Caution is recommended when using diclofenac in patients with mild to moderate hepatic impairment. Method of administration: Intramuscular or intravenous administration.

Use during pregnancy and lactation

Suppression of prostaglandin synthesis can adversely affect the course of pregnancy and intrauterine development of the fetus. Data from epidemiological studies indicate an increased risk of miscarriage and/or the development of heart defects and gastroschisis after taking prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular disease increases from less than 1% to 1.5%. The risk is believed to increase with increasing dose and duration of therapy. It has been shown that in animals, the administration of prostaglandin synthesis inhibitors leads to disruption of embryo implantation. In addition, in animals receiving a prostaglandin synthesis inhibitor during the period of organogenesis, the incidence of various developmental defects, including developmental disorders of the cardiovascular system, increased. Diclofenac should not be prescribed during the first two trimesters of pregnancy unless the benefit outweighs the risk to the fetus. If, after all, Naklofen is used by a woman in the first or second trimester of pregnancy, then the dose should be minimal, and the duration of treatment should be ? as short as possible. As with other NSAIDs, use of the drug during the third trimester of pregnancy is contraindicated. When taking prostaglandin synthesis inhibitors in the third trimester of pregnancy, the fetus may have: 1) premature closure of the ductus arteriosus and pulmonary hypertension, 2) renal dysfunction, with the progression of which renal failure with oligohydroamnion develops. When taking diclofenac at the end of pregnancy, weak labor may develop and the duration of labor may increase. In the mother and in the fetus/newborn, bleeding time may be prolonged; the antiaggregation effect may occur even after taking very low doses of diclofenac. Therefore, diclofenac is contraindicated during the third trimester of pregnancy. Lactation Like other NSAIDs, small amounts of diclofenac are excreted in breast milk. Therefore, diclofenac should not be used during breastfeeding to avoid unwanted effects in the baby. Effects on fertility The use of diclofenac sodium may impair female fertility and is not recommended for women trying to conceive. In women experiencing difficulty conceiving, or with a suspected diagnosis of infertility, treatment with diclofenac sodium should be discontinued. Effect on the ability to drive vehicles and equipment Naklofen has a slight or moderate effect on the ability to drive vehicles and machines. Patients who experience dizziness and/or other undesirable central nervous system effects while taking diclofenac should not drive or operate hazardous machinery.

Precautionary measures

Side effects of the drug can be reduced by using the lowest effective dose for the shortest period necessary to relieve symptoms. Co-administration of Naklofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of evidence of synergistic effects and the occurrence of potentially dangerous additive effects. If there are medical indications, it is recommended to prescribe treatment to elderly patients with caution. In particular, treatment should be started with the lowest effective dose of the drug, especially in frail elderly patients or those with low body weight. As with other NSAIDs, diclofenac may in rare cases cause allergic reactions, including anaphylactic/anaphylactoid reactions. Like other NSAIDs, due to its pharmacodynamic properties, diclofenac can mask the signs and symptoms of infectious diseases. Effect on the gastrointestinal tract When taking NSAIDs, including diclofenac, gastrointestinal bleeding, ulceration or perforation, sometimes fatal, was observed regardless of the period of treatment and was accompanied or not accompanied by symptoms and a history of serious gastrointestinal disorders. They tend to have more serious consequences in older people. If ulcers or gastrointestinal bleeding occur in patients receiving diclofenac, the drug should be discontinued. As with other NSAIDs, including diclofenac, medical supervision is necessary, and particular caution should be exercised when prescribing diclofenac in patients with symptoms suggestive of gastrointestinal disorders, patients with a history of gastric or intestinal ulcers, bleeding or perforation. The risk of gastrointestinal bleeding increases with increasing dose of NSAIDs, especially in patients with a history of ulcers complicated by hemorrhage or perforation. Elderly patients have a higher incidence of adverse reactions when taking NSAIDs, especially gastrointestinal bleeding and perforation, sometimes fatal. To reduce the risk of gastrointestinal toxicity in patients with a history of peptic ulcers (complicated by bleeding or perforation) and in elderly patients, treatment should begin with the lowest effective dose of the drug. These patients should consider combination therapy with protective agents (for example, misoprostol or proton pump inhibitors), as well as patients taking drugs containing low doses of acetylsalicylic acid (acetylsalicylic acid/aspirin drugs increase the risk of gastrointestinal disorders). Patients, especially older patients, should report any unusual abdominal symptoms (especially bleeding) to their doctor. Caution should be exercised when prescribing Naklofen to patients concomitantly taking medications that may increase the risk of bleeding and ulcers, such as systemic corticosteroids, anticoagulants, selective serotonin reuptake inhibitors or antiplatelet agents. Careful medical supervision is necessary for patients suffering from ulcerative colitis or Crohn's disease, since the course of these diseases may worsen. Effect on the liver Careful medical supervision is necessary for patients with impaired liver function, because. their condition may worsen. During therapy with diclofenac, an increase in the activity of liver enzymes may be observed. Diclofenac should be discontinued immediately if elevated liver enzymes persist or increase, clinical signs suggestive of liver disease, or other manifestations (eg, eosinophilia, rash) appear. With long-term use of diclofenac, regular monitoring of liver function is recommended. When taking diclofenac, hepatitis may occur without previous symptoms. Caution should be exercised when prescribing diclofenac to patients with hepatic porphyria, because this may cause an exacerbation of the disease. Effect on renal function Cases of fluid retention and edema have been reported when taking NSAIDs, including diclofenac. Particular caution should be exercised in patients with impaired cardiac or renal function, in patients with a history of hypertension, in elderly patients receiving concomitant therapy with diuretics or drugs that may significantly affect renal function and in patients with significant extracellular volume depletion. associated with various reasons, for example, before or after major surgery. When prescribing diclofenac, regular monitoring of renal function is recommended. Canceling therapy is usually accompanied by normalization of their functions. Effects on the skin and subcutaneous tissue In rare cases, serious skin reactions, some fatal, have been reported with the use of NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Patients are at greatest risk at the beginning of therapy: in most cases, reported adverse reactions occurred in the first month of treatment. Treatment with Naklofen should be stopped at the first signs of skin and mucous rashes, as well as other signs of hypersensitivity. Effect on the cardiovascular and cerebrovascular systems Patients with arterial hypertension and/or mild congestive heart failure require careful monitoring due to the possible development of fluid retention and edema during treatment with non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Results from clinical trials and epidemiological data suggest an increased risk of arterial thromboembolic complications (eg, myocardial infarction or stroke) associated with the use of diclofenac, especially at high doses (150 mg per day) and during long-term treatment. In patients at high risk of cardiovascular events (for example, hypertension, hyperlipidemia, diabetes mellitus, smoking), diclofenac is prescribed only after a thorough examination. The risk of cardiovascular events depends on the dose and duration of treatment with diclofenac; therefore, the lowest effective dose and shortest duration of treatment should be used. Depending on the relief of symptoms and the patient's condition, the dosage of the drug should be periodically reviewed. Hematological effects It is recommended to prescribe diclofenac only for a short period. During long-term therapy, careful monitoring of blood counts is necessary. Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with disturbances in the hemostatic system should be carefully monitored. Pre-existing asthma In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (ie, nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory tract infections (especially those associated with allergic rhinitis or having similar symptoms) more often than other patients, exacerbations of bronchial asthma (so-called analgesic intolerance), Quincke's edema or urticaria occur. Therefore, such patients, as well as patients suffering from allergies to other substances with skin reactions, itching or urticaria, are advised to take special precautions. Information on excipients 3 ml of solution (one ampoule) contains 120 mg of benzyl alcohol. Benzyl alcohol is contraindicated in newborns and children under 3 years of age. In susceptible individuals, especially those with a history of asthma or allergies, metabisulfite may cause allergic-type reactions, including symptoms of anaphylactic reaction and bronchospasm. Naklofen contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially “sodium-free.”

Interaction with other drugs

Lithium: Coadministration may increase plasma concentrations of lithium. Therefore, monitoring serum lithium levels is recommended. Digoxin: Coadministration may increase plasma concentrations of digoxin. Therefore, monitoring serum digoxin levels is recommended. Diuretics and antihypertensive drugs: Like other NSAIDs, co-administration of diclofenac with diuretics or antihypertensive drugs (for example, beta blockers, angiotensin-converting enzyme inhibitors (ACE)) may result in a decrease in their antihypertensive effect. Therefore, when combining these drugs, caution should be exercised, especially in elderly patients, and periodic monitoring of blood pressure is also necessary. After the start of concomitant therapy and periodically during its further continuation due to the increased risk of developing a sufficient amount of fluid while taking diuretics with potassium-sparing drugs in the blood serum. Therefore, frequent monitoring of potassium levels is necessary. Other NSAIDs and corticosteroids: Concomitant use of diclofenac and other systemic NSAIDs or corticosteroids may increase the incidence of adverse gastrointestinal effects. Anticoagulants and antiplatelet agents: It is recommended to use with caution, because coadministration may increase the risk of bleeding. Despite the fact that clinical studies have not revealed the effect of diclofenac on the action of anticoagulants, there are isolated reports of an increased risk of bleeding in patients receiving diclofenac and anticoagulants simultaneously. Such patients should be carefully monitored. Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding. Antidiabetic drugs: Clinical studies have shown that diclofenac does not interfere with the clinical effects of oral antidiabetic drugs. However, there are isolated reports of hypoglycemic and hyperglycemic effects requiring changes in the dosage of antidiabetic drugs during treatment with diclofenac. Therefore, glucose monitoring is recommended as a precaution during concomitant therapy. Methotrexate: Diclofenac may inhibit tubular renal clearance of methotrexate and thereby increase its levels. During concomitant therapy, it is recommended to use NSAIDs, including diclofenac, with caution. Since diclofenac can increase the concentration and, therefore, the toxicity of methotrexate, this drug is administered at least 24 hours before or after treatment with methotrexate. Cyclosporines: Diclofenac, like other NSAIDs, may increase nephrotoxicity due to its effect on renal prostaglandins. Diclofenac is recommended to be administered in doses lower than those that would be used in patients not receiving cyclosporines. Quinolone antibacterials: There have been isolated reports of seizures, which may have been associated with the concomitant use of quinolones and NSAIDs. Phenytoin: When taking phenytoin together, periodic monitoring of phenytoin plasma concentrations is recommended due to the possible increase in phenytoin. Colestipol and cholestyramine: These substances may delay or reduce the absorption of diclofenac. It is therefore recommended that diclofenac be administered at least one hour before or 4 to 6 hours after colestipol/cholestyramine administration. Potent CYP2C9 inhibitors: It is recommended to use diclofenac with caution with strong CYP2C9 inhibitors (for example, sulfinpyrazone and voriconazole), because Significant increases in maximum plasma concentration and exposure of diclofenac may occur due to inhibition of its metabolism. Use with caution with other drugs known to be hepatotoxic, for example, antibiotics, antiepileptic drugs.

Contraindications

Hypersensitivity to diclofenac, sodium metabisulfite, or other components of the drug. Like other non-steroidal anti-inflammatory drugs, diclofenac is contraindicated in patients in whom hypersensitivity to salicylates or other prostaglandin synthesis inhibitors manifests itself in the form of bronchial asthma, urticaria or rhinitis. Liver failure (Child - Pugh Class C) (liver cirrhosis and ascites). Renal failure (creatinine clearance

Compound

3 ml of solution (1 ampoule) contains: Active substance: diclofenac sodium 75 mg. Excipients: benzyl alcohol, propylene glycol, sodium metabisulfite, sodium hydroxide, water for injection.

Overdose

Symptoms There is no typical clinical picture for an overdose of diclofenac. Overdose may cause symptoms such as vomiting, gastrointestinal symptoms, diarrhea, dizziness, tinnitus, or seizures. In case of severe poisoning? acute renal failure, possible liver damage. Therapeutic measures Treatment of acute poisoning with NSAIDs, including diclofenac, consists of supportive and symptomatic therapy. Supportive and symptomatic therapy should be carried out for complications such as hypotension, renal failure, convulsions, gastrointestinal disorders, and respiratory depression. Special measures such as forced diuresis, dialysis or hemoperfusion are likely to be ineffective in eliminating NSAIDs, including diclofenac, due to high protein binding and extensive metabolism. Treatment is symptomatic.

Side effect

Side effects that occur during treatment with diclofenac sodium are classified into appropriate groups depending on the frequency of occurrence: very frequent (? 1/10), frequent (? 1/100 to

• Rare: hypersensitivity reactions, anaphylactic and anaphylactoid reactions (including bronchospasm, hypotension, shock);
• Very rare: angioedema (including facial edema).

Mental disorders

• Very rare: disorientation, depression, insomnia, nightmares, irritability, psychotic reactions.

Nervous system disorders

• Frequent: headache, dizziness;
• Rare: dizziness, fatigue;
• Very rare: paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbance, cerebrovascular accident. Visual disorders
• Very rare: blurred vision, blurred vision, diplopia.

Disorders of the hearing organ and labyrinth system

• Frequent vertigo;
• Very rare: tinnitus, hearing loss.

Heart disorders

• Very rare: palpitations, chest pain, heart failure, myocardial infarction.

Vascular disorders

• Very rare: arterial hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders

• Rare: asthma (including shortness of breath);
• Very rare: pneumonia.

Gastrointestinal disorders

• Frequent: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia;
• Uncommon: constipation;
• Rare: Gastritis, gastrointestinal bleeding, hematemesis, melena, hemorrhagic diarrhea, gastrointestinal ulcer with or without bleeding or perforation;
• Very rare: Colitis (including hemorrhagic, exacerbation of ulcerative colitis or Crohn's disease), stomatitis (including ulcerative), glossitis, disorders of the esophagus, stricture-like changes in the small intestine, pancreatitis.

Hepatobiliary system disorders

• Frequent: increased transaminase levels;
• Rare: jaundice, asymptomatic hepatitis, acute hepatitis, chronic active hepatitis, hepatocellular necrosis, cholestasis;

Very rare: fulminant hepatitis, liver failure. Skin and subcutaneous tissue disorders

• Common: rash;
• Rare: urticaria;
• Very rare: bullous reactions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura, allergic purpura, itching.

Renal and urinary tract disorders

• Very rare: renal failure, acute renal failure, hematuria, interstitial nephritis, nephrotic syndrome, papillary necrolysis, proteinuria.

General disorders and disorders at the injection site

• Common: reaction at the injection site, pain at the injection site, hardening at the injection site;

Rare: swelling, necrosis at the injection site. Infections and infestations

• Very rare: abscess at the injection site.

Clinical trial and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg daily), over long periods of time, may be associated with a modest increase in the risk of arterial thrombosis (eg, risk of myocardial infarction or stroke). . If serious adverse effects occur, treatment should be discontinued.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of the reach of children.

Indications for use of the drug Naklofen

Diseases whose treatment requires anti-inflammatory and/or analgesic action:

• inflammatory rheumatic diseases: rheumatoid arthritis, seronegative spondyloarthritis, chronic juvenile arthritis, arthritis of various etiologies;
• degenerative rheumatism of the joints and spine: arthrosis, spondylosis;
• arthritis caused by metabolic disorders: gout and pseudogout;
• extra-articular manifestations of rheumatism: periarthritis, bursitis, myositis, tendonitis, synovitis;
• other lesions of the musculoskeletal system, accompanied by inflammation and pain;
• as an analgesic for primary and secondary dysmenorrhea, in the postpartum period, for renal and biliary colic, soft tissue injuries, in the postoperative period and after various dental procedures.

Use of the drug Naklofen

For adults with acute pain syndrome, Naklofen is prescribed 3 ml of solution intramuscularly (contents of 1 ampoule) 1–2 times a day for a short time, followed by switching to oral administration or rectal administration of the drug. For patients with pain syndrome due to renal colic, a second injection at a dose of 75 mg can be prescribed 30 minutes after the first. Parenteral administration of the drug to children is not recommended. The tablets are taken orally during or after meals without chewing, with a small amount of water. Adults are prescribed an initial dose of 100–150 mg/day, depending on the severity of the disease; the usual maintenance dose is 100 mg/day. Children over 14 years of age are prescribed a daily dose of 100 mg, which must be divided into 2 doses. If taking Naklofen tablets is combined with the use of other dosage forms, the total daily dose of the drug should be taken into account. The daily dose of diclofenac is 150 mg and depends on the severity of the disease. At the beginning of treatment, 1 capsule of Naklofen Duo is prescribed 1-2 times a day. In case of severe symptoms, especially in the morning, the daily dose (2 capsules) can be taken in one dose or after a short period of time. Maintenance dose - 1 capsule per day. If taking Naklofen Duo capsules is combined with its other pharmaceutical forms, the total daily dose of the drug should be taken into account, which should not exceed 150 mg. Capsules should be swallowed whole with a small amount of liquid during or immediately after meals. Retard tablets are prescribed 1 tablet per day. For patients who do not tolerate oral administration of the drug, it can be prescribed in suppository form. The initial dose is 100–150 mg/day, usually 1 rectal suppository of 50 mg 2–3 times a day. The usual maintenance dose is 1 suppository of 50 mg 2 times a day. Suppositories are not indicated for use in children.

Naklofen tablets po enteric soluble 50 mg No. 10x2

Name

Naklofen tablet entericsol. obol. 50 mg per blister. in pack №10x2

Description

Extended-release tablets, reddish-brown, smooth, round, biconvex, film-coated.

Main active ingredient

Diclofenac

Release form

tab., cover enteric coated, 50 mg: 20 pcs. Reg. No.: 9321/94/99/04/10/15 from 12/03/2015 - Active Tablets, enteric-coated, brown-yellow in color, smooth, round, slightly biconvex. 1 tab. diclofenac sodium 50 mg Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, povidone K25, colloidal anhydrous silicon dioxide, magnesium stearate, hypromellose, red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), copolymer methacrylic acid and ethyl acrylate, propylene glycol, talc. 10 pieces. - blisters (2) - cardboard packs. The drug is available with a prescription tablet. long-acting, covering coated, 100 mg: 20 pcs. Reg. No.: 9322/94/99/04/10/15 from 12/03/2015 - Active Long-acting tablets, coated, reddish-brown, smooth, round, biconvex. 1 tab. diclofenac sodium 100 mg Excipients: sucrose, hypromellose, cetyl alcohol, colloidal anhydrous silicon dioxide, talc, povidone K30, magnesium stearate, titanium dioxide, red iron oxide (E172), macrogol 6000, polysorbate 80. 10 pcs. - blisters (2) - cardboard packs.

Dosage

50 mg

special instructions

During treatment with diclofenac, patients with a history of upper gastrointestinal diseases should be carefully monitored by their physician. Prescribe the drug with caution to patients with ulcerative colitis and Crohn's disease due to the risk of exacerbation of diseases; patients with renal failure or severe liver failure, bleeding disorders, epilepsy, porphyria, as well as patients receiving anticoagulants or fibrinolytics. With long-term use of diclofenac, it is possible, although in rare cases, to develop serious hepatotoxic reactions, therefore it is recommended to regularly examine liver function during treatment. In infectious diseases, the anti-inflammatory and antipyretic effects of diclofenac may mask the symptoms of these diseases. Patients with arterial hypertension and/or mild to moderate congestive heart failure require careful monitoring due to the possible development of fluid retention and edema during treatment with non-selective NSAIDs. Clinical trial and epidemiological data suggest that long-term use of diclofenac, especially at high doses (150 mg daily), may be associated with a modest increase in the risk of arterial thrombosis (eg, risk of myocardial infarction or stroke). Particular caution should be exercised when prescribing the drug to patients with uncontrolled arterial hypertension, congestive heart failure, established coronary artery disease, peripheral vascular disease and/or cerebrovascular disease. A careful analysis should be carried out before long-term administration of the drug to patients with risk factors for developing cardiovascular complications (for example, arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). In elderly patients, Naklofen should be used in the minimum effective dose. The injection solution contains benzyl alcohol, which is contraindicated in newborns and children under 3 years of age. In susceptible people, especially those with a history of asthma or allergies, the metabisulfite in the injection form may cause allergic-type reactions, including symptoms of anaphylactic reaction and bronchospasm. Effect on the ability to drive vehicles and operate machinery. No influence on the ability to drive vehicles and operate machinery has been established.

Pharmacodynamics

Absorption After oral administration, diclofenac sodium is rapidly absorbed. Over 90% of the drug is absorbed, but due to metabolism during the initial passage through the liver, bioavailability is about 60%. After oral administration, the maximum concentration in the blood plasma is achieved within 1-4 hours, depending on the type of drug. Since diclofenac sodium is absorbed in the small intestine, food intake reduces the rate of absorption, which leads to a delay and decrease in the maximum concentration of the active substance in the blood plasma. Although food intake reduces the rate of absorption, the volume of absorption is not reduced. After repeated use of the drug, food intake has no effect on the levels of diclofenac sodium in the blood plasma. Distribution 99% of diclofenac sodium is bound to plasma proteins, mainly albumin. Diclofenac sodium easily penetrates into the synovial fluid, where its concentration reaches 60–70% of the level in the blood serum. After 3–6 hours, the concentration of the active substance and its metabolites in the synovial fluid is higher than in the blood serum. Diclofenac sodium is eliminated from synovial fluid much more slowly than from blood serum. Metabolism and elimination The half-life is 1–2 hours. In mild renal or hepatic insufficiency, this time remains unchanged. Diclofenac sodium is almost completely metabolized in the liver, mainly by hydroxylation and methoxylation. Approximately 70% of diclofenac sodium is excreted in the urine in the form of pharmacologically inactive metabolites. Only 1% of the drug is excreted unchanged. The remaining metabolites are excreted in bile and feces. In elderly patients, significant changes in absorption, distribution, metabolism and excretion are not observed.

Pharmacokinetics

Naklofen is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic properties. It inhibits the activity of cyclooxygenase and thereby inhibits the synthesis of prostaglandins. During treatment with diclofenac sodium, decreased levels of prostaglandins were found in urine, gastric mucosa and synovial fluid. Naklofen is used to treat all forms of rheumatic diseases, as well as to reduce pain of various origins.

Indications for use

Inflammatory and degenerative diseases of the musculoskeletal system, accompanied by pain: inflammatory diseases of the musculoskeletal system (including rheumatoid arthritis, seronegative spondyloarthritis, arthritis of other etiologies); degenerative diseases of the musculoskeletal system (arthrosis, spondylosis); microcrystalline arthritis (including gouty arthritis, pseudogouty arthritis); extra-articular rheumatism; other inflammatory diseases of the musculoskeletal system, accompanied by pain. Pain syndrome of various origins: with soft tissue injuries; in dentistry; after surgical interventions; primary and secondary algodismenorrhea; renal colic; biliary colic; in the postpartum period in the absence of breastfeeding.

Directions for use and doses

Enteric-coated tablets are taken orally during or immediately after meals, swallowed whole and washed down with liquid. Adults are prescribed an initial dose of 100-150 mg/day (1 tablet 2-3 times/day) depending on the severity of the disease. The maintenance dose is usually 100 mg/day. When combining tablets with other dosage forms of Naklofen, the total daily dose of the drug should be taken into account, which should not exceed 150 mg. For children over 1 year of age with juvenile arthritis, the drug is prescribed in a daily dose of 1-3 mg/kg body weight in 2-3 doses. Extended-release tablets Take orally during or immediately after a meal, swallowing whole with liquid. Prescribed for adults. The initial and maintenance dose is 1 tablet. (100 mg) per day. If it is necessary to increase the dose to 150 mg/day, extended-release tablets can be combined with Naklofen in the form of enteric-coated tablets, 50 mg, or Naklofen in the form of rectal suppositories 50 mg. This dosage form is not intended for use in children. Rectal suppositories When combined with other dosage forms of Naklofen, the total daily dose of the drug should be taken into account, which should not exceed 150 mg. Patients who do not tolerate oral dosage forms of the drug can be prescribed rectal suppositories. For adults, the initial dose is 100-150 mg/day (1 supp. 2-3 times/day) depending on the severity of the disease. The maintenance dose is usually 100 mg/day (1 sup. 2 times/day). This dosage form is not intended for use in children.

Use during pregnancy and lactation

Despite the fact that diclofenac does not have a teratogenic effect, use in pregnant women is possible only when the expected benefit outweighs the potential risk to the fetus. Diclofenac is not recommended for use during the third trimester of pregnancy and during breastfeeding.

Precautionary measures

Naklofen may reduce symptoms of an infection (eg, headache, fever), making it difficult to diagnose. If you feel unwell and plan to see your doctor, be sure to tell him or her that you are taking Naklofen. Elderly patients Side effects, especially gastrointestinal, are more common in older people

Interaction with other drugs

When Naklofen is used simultaneously with lithium or digoxin, their concentrations in the blood plasma may increase. With simultaneous use of Naklofen (as well as other NSAIDs) with some diuretics, the diuretic effect is reduced. The combined use of Naklofen and potassium-sparing diuretics can lead to an increase in potassium levels in the blood plasma. The combined use of Naklofen with acetylsalicylic acid and other NSAIDs may lead to the risk of developing undesirable effects. Cyclosporine increases the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which is manifested by increased nephrotoxicity. Naklofen, when used simultaneously, increases the toxicity of methotrexate. Naklofen reduces the effectiveness of antihypertensive drugs. Diclofenac usually does not affect the activity of oral antidiabetic agents. It is not recommended to mix Naklofen in the form of an injection solution with other drugs.

Contraindications

peptic ulcer of the stomach and duodenum in the acute phase; gastrointestinal bleeding; severe heart failure; inflammatory diseases and bleeding in the anorectal area; children's age (for extended-release tablets, rectal suppositories, for injection solution); hypersensitivity to diclofenac or other components of the drug, to salicylates or other NSAIDs, manifested by bronchial asthma, urticaria or rhinitis.

Compound

1 enteric-coated tablet. Active substance: diclofenac sodium 50 mg. Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, povidone K 25, colloidal anhydrous silicon dioxide, magnesium stearate, hypromellose, red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), methacrylic acid ethyl acrylate copolymer , propylene glycol, talc.

Overdose

When administered rectally, an overdose is unlikely. Symptoms: possible nausea, vomiting, epigastric pain, dizziness, tinnitus, irritability, bloody vomiting, melena, impaired consciousness, impaired liver function, respiratory depression, convulsions, renal failure. Treatment: when taken orally, gastric lavage. Carrying out symptomatic therapy. There is no specific antidote. Forced diuresis and hemodialysis are ineffective.

Side effect

Adverse reactions are divided according to frequency: very frequent - >1/10 (10%); frequent - >1/100, but 1%, but 1/1000, but 0.1%, but 1/10,000, but 0.01%, but

Storage conditions

The drug should be stored out of the reach of children, protected from moisture, at a temperature not exceeding 25°C.

Side effects of the drug Naklofen

Possible side effects from the gastrointestinal tract (nausea, abdominal pain, diarrhea, constipation, dyspepsia and flatulence), headache, dizziness, which, as a rule, do not require cessation of treatment. Very rarely possible: bleeding, ulcers and perforation of the gastrointestinal tract, asymptomatic hepatitis, jaundice, acute hepatitis, chronic active hepatitis, hepatocellular necrosis and cholestasis, skin rash, itching, peripheral edema (swelling of the extremities), depression, insomnia, fatigue, anxiety , irritability or drowsiness, renal failure, hematuria. In isolated cases, the development of nonspecific hemorrhagic colitis, relapse or worsening of ulcerative colitis or the appearance of Crohn's disease, hypersensitivity reactions (bronchospasm, angioedema, anaphylactic shock), photosensitivity, anemia, thrombocytopenia, leukopenia and agranulocytosis are observed.

Special instructions for the use of Naklofen

For patients with a history of gastrointestinal bleeding, diclofenac is prescribed only in urgent cases, under close medical supervision, with the simultaneous use of antiulcer drugs. Caution is also required when prescribing Naklofen to patients with ulcerative colitis and Crohn's disease, since diclofenac can cause a relapse or exacerbation of the disease. Diclofenac is prescribed with caution to patients with renal, hepatic or heart failure, patients with epilepsy, porphyria, impaired hemostasis, as well as patients who have been treated with anticoagulants or fibrinolytics. In elderly patients, diclofenac should be prescribed at the minimum effective dose. Although diclofenac has not been experimentally established to have teratogenic properties, the drug should not be prescribed during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus. It is especially not recommended to prescribe the drug in the third trimester of pregnancy, since the blockade of prostaglandin synthesis caused by it can lead to premature closure of the ductus arteriosus. It is recommended to stop breastfeeding while taking the drug. The drug may slightly affect the patient’s ability to drive and operate machinery. Patients with dizziness and central nervous system disorders should refrain from driving vehicles and working with potentially dangerous mechanisms.

Naklofen (table p.kish.r-rim.o. 50 mg N20) Slovenia KRKA, d.d., Novo mesto

NAKLOFEN

Release form, composition and packagingTablets, enteric film coated 1 tablet. diclofenac sodium 50 mg

10 - contour cell packaging (2) - cardboard packs.

pharmachologic effect

NSAID, phenylacetic acid derivative. It has a pronounced anti-inflammatory, analgesic and moderate antipyretic effect. The mechanism of action is associated with inhibition of the activity of COX, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins, which play a major role in the pathogenesis of inflammation, pain and fever. The analgesic effect is due to two mechanisms: peripheral (indirectly, through suppression of prostaglandin synthesis) and central (due to inhibition of prostaglandin synthesis in the central and peripheral nervous system).

Inhibits proteoglycan synthesis in cartilage.

For rheumatic diseases, it reduces pain in the joints at rest and during movement, as well as morning stiffness and swelling of the joints, and helps to increase range of motion. Reduces post-traumatic and postoperative pain, as well as inflammatory swelling.

Suppresses platelet aggregation. With long-term use it has a desensitizing effect.

When applied topically in ophthalmology, it reduces swelling and pain during inflammatory processes of non-infectious etiology.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract. Eating slows down the rate of absorption, but the degree of absorption does not change. About 50% of the active substance is metabolized during the 'first pass' through the liver. When administered rectally, absorption occurs more slowly. The time to reach Cmax in plasma after oral administration is 2-4 hours depending on the dosage form used, after rectal administration - 1 hour, intramuscular administration - 20 minutes. The concentration of the active substance in plasma is linearly dependent on the dose applied.

Does not accumulate. Plasma protein binding is 99.7% (mainly with albumin). Penetrates into synovial fluid, Cmax is reached 2-4 hours later than in plasma.

It is extensively metabolized to form several metabolites, of which two are pharmacologically active, but to a lesser extent than diclofenac.

Systemic clearance of the active substance is approximately 263 ml/min. T1/2 from plasma is 1-2 hours, from synovial fluid - 3-6 hours. Approximately 60% of the dose is excreted in the form of metabolites by the kidneys, less than 1% is excreted unchanged in the urine, the rest is excreted in the form of metabolites in bile.

Indications

Articular syndrome (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout), degenerative and chronic inflammatory diseases of the musculoskeletal system (osteochondrosis, osteoarthritis, periarthropathy), post-traumatic inflammation of soft tissues and the musculoskeletal system (sprains, bruises). Pain in the spine, neuralgia, myalgia, arthralgia, pain and inflammation after operations and injuries, pain with gout, migraine, algodismenorrhea, pain with adnexitis, proctitis, colic (bilious and renal), pain with infectious and inflammatory diseases of the ENT -organs

For local use: inhibition of miosis during cataract surgery, prevention of cystoid macular edema associated with removal and implantation of the lens, inflammatory processes of the eye of a non-infectious nature, post-traumatic inflammatory process in penetrating and non-penetrating wounds of the eyeball.

Dosage regimen

For oral administration for adults, a single dose is 25-50 mg 2-3 frequency of administration depends on the dosage form used, the severity of the disease and is 1-3 times, rectally - 1 time / For the treatment of acute conditions or relief of exacerbation of a chronic process, IM is used at a dose of 75 mg.

For children over 6 years of age and adolescents, the daily dose is 2 mg/kg.

Apply externally in a dose of 2-4 g (depending on the area of ​​the painful area) to the affected area 3-4

When used in ophthalmology, the frequency and duration of administration are determined individually.

The maximum daily dose for adults when taken orally is 150 mg/day

Side effect

From the digestive system: nausea, vomiting, anorexia, pain and discomfort in the epigastric region, flatulence, constipation, diarrhea; in some cases - erosive and ulcerative lesions, bleeding and perforation of the gastrointestinal tract; rarely - liver dysfunction. When administered rectally, in isolated cases, inflammation of the colon with bleeding and exacerbation of ulcerative colitis were observed.

From the central nervous system and peripheral nervous system: dizziness, headache, agitation, insomnia, irritability, feeling tired; rarely - paresthesia, visual impairment (blurredness, diplopia), tinnitus, sleep disorders, convulsions, irritability, tremor, mental disorders, depression.

From the hematopoietic system: rarely - anemia, leukopenia, thrombocytopenia, agranulocytosis.

From the urinary system: rarely - renal dysfunction; swelling may occur in predisposed patients.

Dermatological reactions: rarely - hair loss.

Allergic reactions: skin rash, itching; when used in the form of eye drops - itching, redness, photosensitivity.

Local reactions: a burning sensation is possible at the site of intramuscular injection, in some cases - the formation of infiltrate, abscess, necrosis of adipose tissue; with rectal administration, local irritation, the appearance of mucous discharge mixed with blood, and painful defecation are possible; when used externally in rare cases - itching, redness, rash, burning; when applied topically in ophthalmology, a transient burning sensation and/or temporary blurred vision may occur immediately after instillation.

With prolonged external use and/or application to large surfaces of the body, systemic side effects are possible due to the resorptive effect of diclofenac.

Contraindications

Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, the 'aspirin triad', hematopoietic disorders of unknown etiology, hypersensitivity to diclofenac and the components of the dosage form used, or other NSAIDs.

Use during pregnancy and breastfeeding

Use during pregnancy and lactation is possible in cases where the potential benefit to the mother outweighs the potential risk to the fetus or newborn.

special instructions

Use with extreme caution in patients with a history of liver, kidney, gastrointestinal diseases, dyspeptic symptoms, bronchial asthma, arterial hypertension, heart failure, immediately after major surgical interventions, as well as in elderly patients.

If there is a history of allergic reactions to NSAIDs and sulfites, diclofenac is used only in emergency cases. During treatment, systematic monitoring of liver and kidney function and peripheral blood patterns is necessary.

Rectal use is not recommended in patients with diseases of the anorectal region or a history of anorectal bleeding. It should be used externally only on undamaged areas of the skin.

Avoid contact of diclofenac with the eyes (except for eye drops) or mucous membranes. Patients using contact lenses should use eye drops no earlier than 5 minutes after removing the lenses.

Not recommended for use in children under 6 years of age.

During treatment with dosage forms for systemic use, alcohol consumption is not recommended.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, the speed of psychomotor reactions may decrease. If your vision becomes blurred after using eye drops, you should not drive a car or engage in other potentially hazardous activities.

Drug interactions

When used simultaneously with diclofenac, antihypertensive drugs may weaken their effect.

There are isolated reports of the occurrence of seizures in patients taking NSAIDs and quinolone antibacterial drugs simultaneously.

When used simultaneously with GCS, the risk of side effects from the digestive system increases.

With simultaneous use of diuretics, the diuretic effect may be reduced. When used simultaneously with potassium-sparing diuretics, it is possible to increase the concentration of potassium in the blood.

When used simultaneously with other NSAIDs, the risk of side effects may increase.

There are reports of the development of hypoglycemia or hyperglycemia in patients with diabetes mellitus who used diclofenac simultaneously with hypoglycemic drugs.

When used simultaneously with acetylsalicylic acid, the concentration of diclofenac in the blood plasma may decrease.

Although clinical studies have not established the effect of diclofenac on the action of anticoagulants, isolated cases of bleeding have been described with the simultaneous use of diclofenac and warfarin.

With simultaneous use, it is possible to increase the concentration of digoxin, lithium and phenytoin in the blood plasma.

The absorption of diclofenac from the gastrointestinal tract is reduced when used simultaneously with cholestyramine, and to a lesser extent with colestipol.

With simultaneous use, it is possible to increase the concentration of methotrexate in the blood plasma and increase its toxicity.

With simultaneous use, diclofenac may not affect the bioavailability of morphine, however, the concentration of the active metabolite of morphine may remain elevated in the presence of diclofenac, which increases the risk of developing side effects of the morphine metabolite, incl. respiratory depression.

When used simultaneously with pentazocine, a case of the development of a grand mal seizure has been described; with rifampicin - a decrease in the concentration of diclofenac in the blood plasma is possible; with ceftriaxone - the excretion of ceftriaxone in bile increases; with cyclosporine - increased nephrotoxicity of cyclosporine is possible.

Drug interactions Naklofen

Simultaneous administration of Naklofen with lithium salts or digoxin may cause an increase in their concentration in the blood serum. Naklofen may reduce the diuretic effect of some diuretics; its simultaneous administration with potassium-sparing diuretics can lead to the development of hyperkalemia. When administered simultaneously with acetylsalicylic acid or other NSAIDs, the risk of side effects increases. May enhance the nephrotoxic effect of cyclosporine and the toxic effects of methotrexate, reduce the effectiveness of antihypertensive drugs. Diclofenac generally does not affect the activity of oral hypoglycemic agents.