Diklonat P - instructions for use, dose, side effects, contraindications

Composition:In 1 ampoule contains: active substance diclofenac sodium 75.00 mg; auxiliary substances: disodium edetate 0.20 mg, N-acetylcysteine 2.00 mg, propylene glycol 480.00 mg, macrogol-400 360.00 mg, sodium hydroxide 0.48 mg, water for injection 1206.32 mg.

Description:Transparent from a colorless to slightly yellowish solution.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug.

ATX: & nbsp

S.01.B.C.03 Diclofenac

M.01.A.B.05 Diclofenac

Pharmacodynamics:Diclofenac is a non-steroidal substance belonging to the derivatives of arylacetic acid. It has an anti-inflammatory, analgesic and antipyretic effect. By indiscriminately inhibiting cyclooxygenase, it breaks the metabolism of arachidonic acid, reducing the formation of prostaglandins in the inflammatory focus.

Pharmacokinetics:

Absorption and distribution. The maximum concentration (C_m_Oh) is achieved in plasma after 10-20 minutes and averages 2.7 μg / ml. The degree of absorption is directly proportional to the dose. The area under the "concentration-time" curve after intramuscular (IM) administration is approximately 2 times greater than after its oral or rectal administration, since in the latter cases about half the amount of diclofenac is metabolized by "first passage" through the liver. With subsequent administration of the drug, pharmacokinetic parameters do not change. Provided that the recommended intervals between injections of the drug cumulation is not noted. After 3 hours after administration, the plasma concentrations averaged 10% of the maximum.

The connection with plasma proteins is more than 99% (most of it is associated with albumins). The apparent volume of distribution is 0.12-0.17 l / kg. Diclofenac penetrates into the synovial fluid, where its C_m_Oh is achieved 2-4 hours later than in blood plasma. Apparent half-life (T_1/2) from the synovial fluid is 3-6 hours. 2 hours after reaching C_m_Oh in plasma, the concentration of diclofenac in the synovial fluid is higher than in plasma, and its values remain higher for a period of up to 12 hours.

Metabolism and excretion. The metabolism of diclofenac is partly due to the glucuronization of the unmodified molecule, but mainly through single and multiple hydroxylation and methoxylation, which leads to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5'-hydroxy-, 4', 5-dihydroxy and 3'-hydroxy-4'-methoxydiclofenac), most of which are converted to glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.

The total systemic plasma clearance of diclofenac is 263 ± 56 ml / min. The final T_1/2is 1-2 hours. T_1/2 4 metabolites, including two pharmacologically active, is also short-lived and is 1-3 hours. One of the metabolites, 3'-hydroxy-4'-methoxydiclofenac, has a longer T_1/2, but this metabolite is completely inactive.

About 60% of the dose is excreted by the kidneys in the form of glucuronic conjugates of unchanged active substance, as well as in the form of metabolites, most of which are also glucuronic conjugates. Unchanged, less than 1% of diclofenac is excreted. The rest of the dose of the drug is excreted as metabolites through the intestine.

Pharmacokinetics in special clinical cases. In children, diclofenac concentrations in blood plasma when taking equivalent doses of the drug (mg / kg body weight) are similar to those in adults.

In patients with impaired renal function, when the recommended dosing regimen, cumulation of the unchanged active substance is not noted. When creatinine clearance (CK) is less than 10 ml / min, the calculated equilibrium concentrations of diclofenac hydroxy metabolites are approximately 4 times higher than in healthy volunteers, with the metabolites being excreted exclusively with bile. In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients with preserved liver function.

Indications:

■ Inflammatory and degenerative forms of rheumatic diseases: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis;

■ spine diseases accompanied by pain syndrome;

■ rheumatic diseases of extraarticular soft tissues;

■ an acute attack of gout;

■ renal colic;

■ biliary colic;

■ post-traumatic and postoperative pain syndromes, accompanied by inflammation and edema;

■ gynecological diseases accompanied by pain syndrome and inflammation (eg, primary algodismenorea, adnexitis);

■ as an additional remedy for severe infectious and inflammatory diseases of the ear, throat and nose, with a marked pain syndrome, for example, with pharyngitis, tonsillitis, otitis;

■ severe migraine attacks.

Contraindications:Hypersensitivity to diclofenac or to one of the components of the drug; bronchospasm; bronchial asthma; urticaria or acute rhinitis; angioedema or shock when taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs) in anamnesis; peptic ulcer / gastrointestinal bleeding in the active phase or in anamnesis (two or more confirmed cases of an ulcer or bleeding in an anamnesis); presence in the anamnesis of gastrointestinal bleeding or perforated ulcer of the gastrointestinal tract associated with previously conducted therapy with NSAIDs; undiagnosed hemopoiesis or coagulation; cerebrovascular bleeding or other bleeding; severe degree of heart failure; severe violationsliver or kidney function; the last trimester of pregnancy; children's age till 18 years; hypersensitivity to amide local anesthetics; severe conduction disturbances of the myocardium; cardiogenic or hypovolemic shock; bradycardia; condition after aorto-coronary bypass surgery; concomitant use with other NSAIDs.

Carefully:Porphyria, systemic lupus erythematosus, mixed connective tissue diseases; a history of gastrointestinal dysfunction; arterial hypertension; cardiac failure; renal and hepatic impairment; condition after extensive surgical interventions; Pollinosis; chronic obstructive pulmonary disease; bronchial asthma; polypous rhinosinusitis; blood clotting disorders; simultaneous use with drugs of lithium, digoxin, diphenin, angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, preparations affecting cyclooxygenase-2, methotrexate, cyclosporine, glucocorticosteroids, antiplatelet agents, serotonin reuptake inhibitors, antibacterial drugs of the quinolone series.

Pregnancy and lactation:

The inhibition of the synthesis of prostaglandins can have an adverse effect on the course of pregnancy and fetal development. The results of epidemiological studies indicate that when taking inhibitors of prostaglandin synthesis in the early stages of pregnancy, the risk of miscarriage, as well as gastroschisis and anomalies of the cardiac fetus, increases. It is assumed that the risk of pathology increases in proportion to the dose and duration of treatment.

During the first and second trimesters of pregnancy, Diclonate P is not recommended, except in cases of obvious need. If the drug Diclonate P is taken by a woman who is trying to become pregnant, or during the first and second trimester of pregnancy, the dose and duration of therapy should be minimal.

Prostaglandin synthesis inhibitors taken during the third trimester of pregnancy may pose a threat to fetal development and lead to cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension); impaired renal function, which can lead to renal insufficiency with oligohydroamniosis.

At the end of pregnancy, taking any inhibitors of prostaglandin synthesis is dangerous for the mother and fetus because of the possible increase in bleeding time-the antiplatelet effect may appear even in very small doses; oppression of uterine contractions, which can lead to a delay or an increase in the duration of labor. Therapy with Diclonate P is contraindicated in the third trimester of pregnancy and during lactation.

Dosing and Administration:

Intramuscularly. Diclonate P is administered as a single injection of 75 mg (1 ampoule) deep into the muscle. The daily dose should not exceed 150 mg. The duration of treatment is determined by the attending physician, do not use Diclonate P for intramuscular injection for more than 2 consecutive days.

In / m administration of the drug is particularly preferred at the onset of exacerbations of inflammatory and degenerative diseases with high inflammation activity and pain conditions caused by inflammation of non-rheumatic genesis.

If necessary, the continuation of therapy goes to oral, or rectal administration.

For rheumatic diseases, it may be necessary to administer the drug for a long time.

To reduce the likelihood of side effects, Diclonate P should be taken at the lowest effective dose for a short period sufficient to provide a therapeutic effect

Side effects:

Side effects mainly depend on the dosage and vary greatly in patients. Especially it concerns the risk of gastrointestinal bleeding (gastritis, erosion, ulcer), which largely depend on the dose of the drug, and on the duration of treatment.

The frequency of side effects is classified according to the recommendations of the World Health Organization: very often (> 1/10); often (from >1/100 to <1/10); infrequently >1/1000 to <1/100); rarely (from >1/10000 to <1/1000); very rarely (<1/10000); the frequency is unknown - it is impossible to determine from the available data.

From the side of the circulatory and lymphatic systems: very rarely - violations of hemopoiesis (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis), hemolytic anemia. Patients on long-term treatment with NSAIDs should be given regular blood tests.

From the immune system: often - allergic reactions (such as skin itching or skin rash); infrequently - hives; very rarely - allergic vasculitis, pulmonitis, severe allergic reactions.Can manifest as a facial edema, swelling of the tongue and posterior pharynx with narrowing of the airways, shortness of breath, tachycardia and a drop in blood pressure, sometimes anaphylactic shock can develop.

From the nervous system: often - headache, dizziness, irritability or fatigue; very rarely - disorders of sensitivity, disorders of taste sensitivity, memory disorders, disorientation, convulsions, tremor, psychotic reactions, depression, anxiety, nightmares.

From the side of the organ of vision: very rarely - blurred vision, diplopia, decreased vision.

From the side of the hearing organ and labyrinthine disorders: often - vertigo; very rarely - "ringing" in the ears, hearing loss.

From the side of the cardiovascular system: very rarely - hypertension, palpitation, chest pain, myocardial infarction, cardiac arrest.

From the digestive tract: very often - gastrointestinal disorders (nausea, vomiting, diarrhea, minor gastrointestinal bleeding, in some cases leading to anemia); often - dyspepsia, flatulence, colic and abdominal pain, loss of appetite,gastrointestinal ulcers (in some cases accompanied by bleeding and perforation); infrequently - gastritis, bloody vomiting, melena, bloody diarrhea; very rarely - stomatitis, glossitis, lesions of the esophagus, dysfunction of the lower gastrointestinal tract (hemorrhagic colitis), exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis.

On the part of the liver function: often - increased levels of "liver" transaminases in the serum; rarely - violations of the liver, especially with long-term treatment, acute hepatitis, accompanied by jaundice or without jaundice (in very rare cases with instant development without noticeable prodromal symptoms with the development of hepatic coma and liver necrosis).

From the skin: often - skin rash; very rarely - exanthema, eczema, erythema, hair loss, sensitivity to light, purpura (including allergic), bullous reactions (including Stevens-Johnson syndrome) and toxic epidermal necrolysis, bullous dermatitis, toxic epidermal necrolysis (Lyell's syndrome).

From the side of the kidney and urinary tract system, Very rarely - renal failure and urinary pathology (hematuria, proteinuria, interstitial nephritis, nephrotic syndrome and papillary necrosis),decreased urinary output.

Other: often - the reaction at the injection site; infrequently - edema (especially in patients with arterial hypertension or renal insufficiency); rarely - aseptic necrosis, necrosis of adipose tissue; very rarely - an abscess at the injection site. In very rare cases, patients who systematically take NSAIDs have been aggravated by inflammatory conditions of infectious genesis (development of necrotizing fasciitis). If during the treatment with Diklonat P the patient develops an infectious disease or relapses of an existing infectious disease, the patient should immediately seek appropriate medical assistance and, if necessary, be treated with antibacterial drugs.

Very rarely, when treated with Diclonate P, patients were diagnosed with signs of aseptic meningitis, such as stiff neck, nausea, vomiting, fever, or blurred vision. According to available data, patients suffering from autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease) may be predisposed to such symptoms.

The results of clinical studies, as well as epidemiological data suggest that therapy with Diclonate P, especially prolonged and in large doses (150 mg / day) may cause a slight increase in the risk of thrombotic

lesions of arterial vessels (eg, myocardial infarction or stroke).

In the treatment of NSAIDs, cases of peripheral edema, hypertension, and heart failure.

Overdose:

Symptoms: dizziness, headache, loss of consciousness, in children myoclonic cramps, abdominal pain, nausea, vomiting, gastrointestinal bleeding, impaired liver and kidney function, respiratory depression, cyanosis.

Treatment: symptomatic therapy to avoid complications such as hypotension, renal failure, convulsions, irritation of the gastrointestinal tract and respiratory depression.

Interaction:

The simultaneous use of diclofenac and other NSAIDs increases the risk of developing gastrointestinal ulcers and bleeding due to the synergistic effect of the drugs, so administer diclofenac concurrent with other NSAIDs is not recommended.

With simultaneous application diclofenac can increase the concentration of lithium (digoxin or diphenine) in the blood plasma, so you need to monitor the concentration of these drugs in the plasma.

Diclofenac can reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg, in patients with dehydration or in the elderly), simultaneous administration of ACE inhibitors or angiotensin II antagonists and drugs depressing cyclooxygenase can lead to further impairment of renal function, increasing the risk of acute renal failure rule, reversible). Therefore, use caution when using diclofenac with these drugs, especially in elderly patients.

Patients should consume a sufficient amount of fluid, it is also advisable to monitor the indicators of renal activity - at the beginning of the combination therapy course and then at a certain interval. With the simultaneous intake of potassium-sparing diuretics, potassium levels in the serum may be raised, so it is necessary to monitor the potassium concentration.

With simultaneous use with diclofenac, the antihypertensive effect of antihypertensive drugs may be reduced.

When used simultaneously with glucocorticosteroids, antiplatelet agents and selective serotonin reuptake inhibitors, the risk of ulceration or the occurrence of gastrointestinal bleeding increases. Caution should be exercised when using diclofenac with less than 24-hour intervals before or after taking methotrexate. Possible cumulation of methotrexate and increasing its toxic properties.

With simultaneous admission with cyclosporine, cases of development of nephrotoxicity were reported. The cause may be a combined anti-prostaglandin effect of diclofenac and cyclosporin on the kidneys.

Diclofenac can enhance the effect of anticoagulants, such as warfarin. Reported hypo- and hyperglycemic effects of diclofenac, which required correction of the dose of antidiabetic drugs. With combined treatment, glucose concentration in the blood should be monitored.

Drugs containing probenecid or sulfinpyrazone may slow the excretion of diclofenac.

As a result of the interaction of antibacterials of quinoline and diclofenac, the risk of seizures increases.

Special instructions:

Avoid simultaneous administration of Diclonate P and other NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2). To reduce the risk of unwanted effects, the drug should be taken at the lowest dose and for a short period, sufficient to achieve a therapeutic effect. In elderly patients against the background of therapy with Diclonate P, the frequency of unwanted side effects increases - gastrointestinal bleeding, perforation of the gastrointestinal mucosa, which can lead to death. Bleeding, ulcers and perforation of the gastrointestinal mucosa, which can lead to death, may occur during therapy with any NSAID. These side effects can occur at any stage of treatment, as in situations of the presence of such symptoms earlier, and in the absence of those in the history.

The elderly, as well as patients who need combination therapy with small doses of aspirin or other drugs,increasing the risk of violations from the gastrointestinal tract, it is advisable to prescribe such drugs as proton pump inhibitors.

Patients with toxic gastrointestinal lesions in history, especially the elderly, should immediately report any uncharacteristic manifestations from the abdominal organs (especially the occurrence of gastrointestinal bleeding) that occur during the initial stages of treatment. Greater caution is required in the treatment of patients taking drugs in parallel, which may increase the risk of developing ulcers or bleeding, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (aspirin). In the case of gastrointestinal bleeding or ulceration, Diclonat P should be discontinued.

Diclonate P should be given with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease) to avoid their exacerbation.

Patients with a history of hypertension and congestive heart failure of mild / moderate

The severity should be monitored regularly, since the treatment with Diclonate P medication may cause fluid retention and swelling.

Clinical studies, as well as epidemiological data, indicate that Diclonate P, especially prolonged and in high doses (150 mg / day), may cause a slight increase in the risk of thrombotic lesions of arterial vessels (eg, myocardial infarction or stroke). Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial and / or cerebrovascular disease should be prescribed diclofenac it is possible only after careful consideration of each specific case. Increased caution should be observed when prescribing long-term therapy with diclofenac to patients with an increased risk of cardiovascular disorders (eg, hypertension, hyperlipidemia, diabetes, smoking and other). Serious skin pathologies, including fatalities, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal

Necrolysis due to NSAID therapy is very rarely diagnosed. The maximum risk of developing such

violations occurs at the very beginning of treatment, in most cases during the first month of therapy with the drug

Diclonate P. If you experience the first skin rashes, signs of mucosal lesions or any other manifestations of hypersensitivity, treatment with Diclonate P should be discontinued. Taking NSAIDs with alcohol can increase unwanted effects of drugs, especially with regard to the gastrointestinal tract and central nervous system.

In patients with congenital impairments of porphyrin metabolism (such as acute intermittent porphyria), systemic lupus erythematosus, and mixed connective tissue disease, the possible benefit and risk of Diclonate P.

With extreme caution, the drug should be prescribed to patients with a history of gastrointestinal disorders suffering from hypertension or heart failure, with impaired renal or hepatic function, and also immediately after major surgical interventions.Since Diclonate P can suppress signs and symptoms of infection, care should be taken when assigning it to patients at risk of infection. Anaphylactic reactions of varying severity are possible with Diclonate P therapy in patients with hypersensitivity to acetylsalicylic acid or other NSAIDs. Patients suffering from hay fever,

chronic obstructive pulmonary disease, pollipozny rhinosinusitis, should be careful when taking Diklonat P, because this group of patients is characterized by an increased risk of allergic reactions (can occur as episodes of bronchospasm, Quincke edema or urticaria). Severe hypersensitivity reactions (eg, anaphylactic shock) are very rare. At the first signs of an allergic reaction, the administration of Diclonate P should be discontinued after appropriate medical manipulation. Diclonate P can temporarily inhibit platelet aggregation, so patients with blood clotting disorders should be closely monitored.

With long-term therapy with Diclonate P, a regular assessment of the level of liver enzymes, renal function, and a blood test is required. Caution should be exercised when prescribing a patient suffering from bronchial asthma or having a history of this disease, since NSAIDs can cause bronchospasm in this group of patients.

With long-term use of analgesics, headaches can occur which are not removed by increasing the dose of the drug. Diclonate P. Combinations of several analgesics can lead to permanent damage to kidney function with the threat of renal failure (analgesic neuropathy).

Effect on the ability to drive transp. cf. and fur:Since diclofenac administration can cause side effects from the central nervous system, such as fatigue or dizziness, in some cases the ability to drive or work with other mechanisms can worsen. Side effects can be especially aggravated in case of simultaneous intake of the drug with alcohol.

Form release / dosage:

Solution for intramuscular injection 75 mg / 2 ml.

Packaging:

2 ml of the drug in a dark glass ampoule (type 1).

1, 3, 5 ampoules into a plastic or cardboard tray. One tray with 1, 3, 5 ampoules or 2 pallets with 5 ampoules together with instructions for use in a cardboard box.

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

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N 015378/01

Date of registration:11.09.2012

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

MERCKLE, GmbH Germany

Representation: & nbspTeva Teva Israel

Information update date: & nbsp08.02.2016

Illustrated instructions

Instructions

Diclonat® P (Diclonat® P)