Sodium diclofenac
Producer: JSC Borisovsky Plant of Medical Supplies Republic of Belarus
Code of automatic telephone exchange: M01AB05
Release form: Liquid dosage forms. Solution for injections.
General characteristics. Structure:
Active ingredient: 75 mg of diclofenac of sodium in 3 ml of solution.
Excipients: propylene glycol, a mannitol, benzyl alcohol, sodium pyrosulphite, sodium hydroxide, water for injections.
Pharmacological properties:
Pharmacodynamics. Sodium diclofenac – derivative phenylacetic acid; has antiinflammatory, analgeziruyushchy and febrifugal effect. Not selectively oppressing TsOG1 and TsOG2, breaks metabolism of arachidonic acid, reduces quantity of Pg in the inflammation center. It is most effective at pains of inflammatory character. As all non-steroidal anti-inflammatory drugs, renders antiagregantny activity.
At rheumatic diseases protivospalitelny and analgetic properties of diclofenac of sodium provide the clinical effect which is characterized by considerable reduction of expressiveness of such symptoms and complaints as pain at rest and at the movement, morning constraint and a swelling of joints, and also function improvement.
In vitro sodium diclofenac, in concentration, equivalent to those which are reached at treatment of patients does not suppress biosynthesis of proteoglycans of cartilaginous tissue.
At the posttraumatic and postoperative inflammatory phenomena sodium diclofenac quickly stops pains (both spontaneous, and arising at the movement), reduces inflammatory hypostasis and hypostasis of a postoperative wound.
The conducted clinical trials allowed to reveal considerable analgetic effect of drug at the moderated and strongly expressed pain syndrome of not rheumatic genesis. Diclofenac of sodium is capable to eliminate pain and to reduce expressiveness of blood loss at primary dysmenorrhea.
Besides, has favorable effect on manifestations of attacks of migraine.
Pharmacokinetics. Absorption. After intramuscular introduction of 75 mg of diclofenac its absorption begins immediately. The maximum concentration in plasma which average value makes about 2.5 mkg/ml (8 µmol/l) is reached approximately in 20 minutes. Right after its achievement bystry decrease in concentration of drug in plasma is observed. The amount of the soaking-up active agent is in linear dependence on drug dose size. Area size under a curve "concentration time" (AUC) after intramuscular administration of medicine is approximately twice more, than after its oral or rectal administration as in prosledny cases about a half of amount of diclofenac is metabolized at "the first passing" through a liver.
After repeated use of drug pharmacokinetic indicators do not change.
On condition of observance of the recommended intervals between administrations of drug of cumulation it is not noted.
Distribution. Linkng with serum proteins (it is preferential with albumine) makes 99,7%. The seeming volume of distribution makes 0,12-0,17 l/kg.
Diclofenac gets into synovial fluid where its maximum concentration is reached at 2-4 o'clock later, than in a blood plasma. The seeming elimination half-life makes 3-6 hours of synovial fluid. In 2 hours after achievement of the maximum concentration in plasma concentration of a diklofeiak in synovial fluid is higher, than in plasma, and its values remain higher throughout a span till 12 o'clock.
Metabolism. Metabolism of diclofenac is carried out partially by a glyukuronization of not changed molecule, but, mainly, by means of a single and repeated metoksilirovaniye that leads to formation of several phenolic metabolites (Z1-gidroksi-, 4-gidroksi-, 5-gidroksi-, 4,5-digidroksi-and 3-hydroxy-4-metoksidiklofenaka), the majority of which turns into glyukuronidny conjugates.
Two of these phenolic a metabolite are biologically active, but in much smaller degree, than diclofenac.
Removal. The general system plasma clearance of diclofenac makes 263±56 ml/min. The final elimination half-life makes 1-2 hours. The elimination half-life of 4 metabolites, including two pharmacological active, is also short and makes 1-3 hours. One of metabolites, 3-hydroxy - 4-метокси-diclofenac, has longer elimination half-life, however this metabolite is completely inactive. About 60% of the applied dose of drug are removed with urine in the form of glucuronic conjugates of not changed active agent, and also in the form of metabolites, the majority of which is represented by glucuronic conjugates. In not changed look less than 1% of diclofenac are removed. The rest of the applied dose of drug is removed in the form of metabolites with bile, with a stake.
Pharmacokinetics at separate groups of patients. At patients with a renal failure at purpose of Diclofenac of sodium in usual single doses of accumulation of diclofenac it was not noted. If the clearance of creatinine makes less than 10 ml/min., settlement equilibrium concentration of hydroxymetabolites of diclofenac are about 4 times higher, than at healthy patients. However, eventually metabolites are removed with bile.
At patients with chronic hepatitis or the compensated cirrhosis indicators of pharmacokinetics of diclofenac are similar to that at patients without liver diseases.
Indications to use:
- inflammatory and degenerative forms of rheumatic diseases (the pseudorheumatism ankylosing a spondylitis, an osteoarthrosis, spondylarthrites);
- pain syndromes from a backbone;
- rheumatic diseases of extraarticular soft tissues;
- bad attack of gout;
- the posttraumatic and postoperative pain syndromes which are followed by an inflammation and hypostasis;
- attacks of migraine of a heavy current;
- renal and bilious colic.
Route of administration and doses:
It is shown for treatment of acute states or stopping of aggravations of chronic process. The adult enter 75 mg (1 ampoule) 1-2 times a day intramusculary (deeply into a gluteus) within no more than 2 days. Then pass to sodium diclofenac reception in tablets or suppositories.
Features of use:
With extra care appoint drug sick with diseases of a liver and kidneys, digestive tract diseases in the anamnesis, dispeptic symptoms at the time of purpose of drug, an arterial hypertension, heart failure, right after serious surgical interventions, and also to patients of advanced age. The patient having in the anamnesis of the instruction on allergic reactions to non-steroidal anti-inflammatory drugs and sulfites, diclofenac of sodium is appointed only in urgent cases.
In the course of treatment by drug systematic control of function of a liver and kidneys, a picture of peripheral blood is necessary.
At sodium diclofenac co-administration with anticoagulants control of a prothrombin time is necessary; the dose of anticoagulant is changed respectively clinical requirements.
Use during the periods of pregnancy and a lactation. During pregnancy use of Diclofenac of sodium is contraindicated. In need of appointment of the nursing mother it is necessary to resolve an issue of the breastfeeding termination.
Influence on ability to drive the car and work with mechanisms. To the patients testing during sodium Diclofenac use dizziness or other unpleasant feelings from the central nervous system including vision disorders, it is not necessary to drive the car or to manage mechanisms.
Side effects:
At assessment of frequency of occurrence of various side reactions the following gradation are used: "often"-> 10%, "sometimes"-> 1-10%, are "rare"-> 0.001-1%, "in some cases" - <0.001%.
From digestive tract: sometimes - pains in epigastric area, nausea, vomiting, diarrhea, spasms in a stomach, dyspepsia, abdominal distention, anorexia; seldom - gastrointestinal bleeding (a hematemesis, a melena, diarrhea with blood impurity), stomach ulcer and intestines, followed or not followed by bleeding or perforation; in some cases - aphthous stomatitis, a glossitis, changes from a gullet, emergence of diafragmopodobny strictures in intestines, disturbances from lower parts of intestines, such as nonspecific hemorrhagic colitis, exacerbation of nonspecific ulcer colitis or disease Krone, locks, pancreatitis.
From the central nervous system: sometimes - a headache, dizziness, the expressed dizziness; seldom - drowsiness; in some cases – sensitivity disturbances, including paresthesias, dysmnesias, a disorientation, sleeplessness, irritability, spasms, a depression, feeling of alarm, nightmares, a tremor, psychotic reactions, aseptic meningitis.
From sense bodys: in some cases - vision disorders (sight misting, a diplopia), hearing disorder, a sonitus, disturbances of flavoring feelings.
Dermatological reactions: sometimes - skin rashes; seldom - a small tortoiseshell; in some cases - rashes in the form of bubbles, eczema, a mnogoformny erythema, Stephens's syndrome - Johnson, a Lyell's disease (an acute toxic epidermolysis), an erythrosis (exfoliative dermatitis), a hair loss, photosensitive reactions; purpura, including allergic.
From kidneys: seldom - hypostases; in some cases - an acute renal failure, changes of an urocheras (a hamaturia and a proteinuria), intersticial nephrite; nephrotic syndrome; papillary necrosis.
From a liver: sometimes - increase in level of aminotransferases in blood serum; seldom - the hepatitis which is followed or not followed by jaundice; in some cases - fulminant hepatitis.
From system of a hemopoiesis: in some cases – thrombocytopenia, a leukopenia, hemolitic anemia, aplastic anemia, an agranulocytosis.
Hypersensitivity reactions: seldom - hypersensitivity reactions, such as bronchial asthma, system anaphylactic/anaphylactoid reactions, including hypotension; in some cases - a vasculitis, a pneumonitis.
From cardiovascular system: in some cases - heartbeat, stethalgias, hypertensia, congestive heart failure.
Others: sometimes - reactions in the place of an intramuscular injection in the form of local pain and consolidation; in some cases - local abscesses and necroses in the place of an intramuscular injection.
Interaction with other medicines:
Lithium, digoxin. Diclofenac of sodium can increase concentration of lithium and digoxin in a blood plasma.
Diuretic means. Sodium diclofenac, also as well as other NPVP, can reduce expressiveness of diuretic action. Simultaneous use of kaliysberegayushchy diuretics can lead to increase in level of potassium in blood serum (in case of such combination of medicines this indicator should be controlled often).
NPVP. Simultaneous system use of NPVP can increase the frequency of emergence of the undesirable phenomena.
Anticoagulants. Though in clinical trials it was not established sodium Diclofenac influences on effect of anticoagulants, there are separate messages on increase in risk of bleedings at the patients accepting at the same time Diclofenac of sodium and these drugs. Therefore, in case of such combination of medicines careful and regular observation of patients is recommended.
Antidiabetic drugs. In clinical trials it is established that perhaps simultaneous use of Diclofenac of sodium and antidiabetic drugs, at the same time efficiency of the last does not change. However, separate messages on development in such cases both a hypoglycemia, and a hyperglycemia are known that caused need of change of a dose of glucose-lowering drugs during sodium Diclofenac use.
Methotrexate. It is necessary to be careful at purpose of NPVP less than in 24 hours prior to or after reception of a methotrexate as in such cases concentration of a methotrexate in blood can increase and amplify its toxic action.
Cyclosporine. Influence of NPVP on synthesis of prostaglandins in kidneys can increase nephrotoxicity of cyclosporine.
Antibacterial agents - derivatives of a hinolon. There are separate messages on development of spasms in the patients receiving at the same time derivative hinolon and NPVP.
Pharmaceutical incompatibility. As a rule, it is not necessary to mix the solution which is contained in ampoules with solutions of other medicines for injections.
Contraindications:
- active gastritis and/or gastroduodenal ulcer, gastrointestinal bleeding or perforation;
- inflammatory diseases of intestines (such as disease Krone and ulcer colitis);
- hypersensitivity to diclofenac and any other ingredients of drug, including to sodium pyrosulphite;
- sodium diclofenac as well as other non-steroidal anti-inflammatory drugs (NPVP), it is contraindicated to those patients who in response to reception of acetylsalicylic acid or other NPVP have attacks of bronchial asthma, urticaria or acute rhinitis;
- diclofenac of sodium is not appointed to children and teenagers aged up to 18 years;
- pregnancy;
- heavy heart failure (NYHA III-IV);
- a heavy liver failure (a class C on Chayld-Pyyu (cirrhosis and ascites));
- hypovolemia and dehydration;
- patients with high risk of postoperative bleeding, against the background of use of anticoagulants, patients with an incomplete hemostasis, patients with disturbance of a hemopoiesis or cerebrovascular bleeding;
- therapy of postoperative pains after aortocoronary shunting and other heart operations.
Overdose:
The typical clinical picture inherent to overdose by medicine, does not exist.
Treatment. Treatment of acute poisoning of NPVP consists in use of the supporting and symptomatic therapy.
The supporting and symptomatic treatment is shown at such complications as: arterial hypotension, a renal failure, spasms, disturbances from digestive tract and respiratory depression. It is improbable that an artificial diuresis, the hemodialysis or hemoperfusion will be useful to removal of NPVP as active agents of these drugs substantially contact proteins of plasma and are exposed to intensive metabolism.
Storage conditions:
In the place protected from light, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to use medicine after the termination of a period of validity.
Issue conditions:
According to the recipe
Packaging:
On 3 ml in ampoules in packaging No. 10, No. 10 x 1, No. 5 x 2.
