for medical use
of DIKLOFENAK-AKOS medicine
the Trade name
the International unlicensed
name Diclofenac Dosage Form Solution for intramuscular introduction, 25 mg/ml
of 1 ml of solution contains
active agent – diclofenac of sodium of 25 mg,
excipients: benzyl alcohol – 40 mg, propylene glycol, Mannitolum – 6 mg, sodium disulphite, 1 M hydroxide sodium solution, water for injections
the Transparent slightly painted liquid with a slight smell of benzyl alcohol
Non-steroidal anti-inflammatory drugs. Acetic acid derivatives. Diclofenac.
The ATX M01AB05 code
Pharmacokinetics Later properties of intramuscular introduction of 75 mg of diclofenac its absorption begins immediately. The maximum concentration in plasma which average value is about 2.5 mkg/ml (8 µmol/l) is reached approximately in 20 minutes. Right after its achievement the fast 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 the drug Diklofenak-AKOS is approximately twice more, than after its oral or rectal administration as in the last cases about a half of amount of diclofenac is metabolized at the first passing through a liver.
After repeated use of drug the pharmacokinetic indicators do not change. On condition of observance of the recommended intervals between administrations of drug of cumulation it is not noted.
Linking with serum proteins makes 99.7%, it happens, mainly to albumine (99.4%). The approximate volume of distribution is 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 blood plasma. Approximate elimination half-life makes 3-6 hours of synovial fluid. In 2 hours after achievement of the maximum concentration in plasma the concentration of diclofenac in synovial fluid is higher, than in plasma, and its values remain higher till 12 o’clock.
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 (3 ‘-hydroxy, 4’ – hydroxy, 5 ‘-hydroxy, 4’, 5-digidroksi- and 3 ‘-hydroxies-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.
The general system plasma clearance of diclofenac is 263±56 ml/min. Final elimination half-life makes 1-2 hours. Elimination half-life of 4 metabolites, including two pharmacological active, is also short and makes 1-3 hours. One of metabolites, 3 ‘-hydroxies-4 ‘-metoksi-diclofenac, has longer elimination half-life, however this metabolite is completely inactive.
About 60% of the accepted 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 accepted dose of drug is removed in the form of metabolites with bile, with a stake and urine.
The pharmacokinetics at separate groups of patients
At some patients of advanced age 15-minute intravenous infusion resulted in concentration, higher for 50%, in plasma, than it was observed at young healthy faces.
At patients with a renal failure when prescribing the drug Diklofenak-AKOS in usual single doses of accumulation of diclofenac it was not noted. However eventually metabolites are removed with bile.
At patients with chronic hepatitis or the compensated cirrhosis the indicators of pharmacokinetics of diclofenac are similar to that at patients without liver diseases.
of Diklofenak-AKOS contains sodium diclofenac, the substance of nonsteroid structure rendering the significant anti-inflammatory, analgetic and febrifugal action. Slowing down of biosynthesis of prostaglandins is considered the main mechanism of effect of diclofenac. Prostaglandins play an important role in genesis of inflammation, pain and fever.
In rheumatic diseases the protivospalitelny and analgetic properties of the drug Diklofenak-AKOS 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.
Diclofenac of sodium does not suppress biosynthesis of proteoglycans of cartilaginous tissue.
At the posttraumatic and postoperative inflammatory phenomena of Diklofenak-AKOS quickly stops pains (both spontaneous, and arising at the movement), reduces inflammatory hypostasis and hypostasis of a postoperative wound.
The considerable analgetic effect of drug at a moderate and severe pain syndrome of not rheumatic genesis is revealed. Diklofenak-AKOS it is capable to eliminate pain at primary dysmenorrhea.
Diklofenak-AKOS, besides, has favorable effect on manifestations of attacks of migraine.
– inflammatory and degenerative forms of rheumatism: the pseudorheumatism ankylosing a spondylitis, an osteoarthritis, a spondylarthritis, a pain syndrome in backbone diseases, extraarticular rheumatism
– a bad attack of gout
– renal or hepatic gripes
– a posttraumatic and postoperative pain syndrome, inflammation and puffiness
– heavy attacks of migraine
the Route of administration and doses
Within the general recommendation the dose of drug has to be appointed individually. Side effects can be minimized by means of use of a minimal effective dose during the minimum period demanded for control over symptoms.
It is not necessary to use an injection the drug Diklofenak-AKOS more than 2 days in a row. If necessary treatment can be continued by means of the drug Diklofenak-AKOS in tablets or rectal candles.
Drug is used at adult patients. The drug is administered intramusculary by a deep injection in rump.
When carrying out an intramuscular injection to avoid injury of nerves or other fabrics to the place of an injection, it is recommended to follow the following rules.
The drug should be administered deeply intramusculary in an upper external quadrant of rump. The dose usually makes 75 mg (contents of 1 ampoule) once a day. In hard cases, as an exception, 2 injections on 75 mg, with an interval in several hours can be carried out (the second injection has to be carried out to opposite rump).
As an alternative, one injection of drug a day (75 mg) can be combined with reception of other dosage forms of the drug Diklofenak-AKOS (tablets, rectal candles), at the same time the maximum daily dose makes 150 mg.
At migraine attacks the clinical experience is limited to use of one ampoule of 75 mg, the dose is entered after use of suppositories on 100 mg on the same day (if necessary). The general daily dose should not exceed 175 mg in the first day.
The geriatrics (patients at age & gt, 65)
Correction of an initial dose is not required for elderly patients.
The established cardiovascular disease or essential risk factors from a cardiovascular system
As a rule, therapy of the drug Diklofenak-AKOS is not recommended to patients with the established cardiovascular disease or an uncontrollable hypertension. If necessary, Diklofenak-AKOS is appointed to patients with the established cardiovascular disease, an uncontrollable hypertension, or essential risk factors of a cardiovascular disease only after thorough examination and only within daily doses ≤ 100 mg in case of therapy lasting over 4 weeks.
Patients with impaired renal function
of Diklofenak-AKOS it is contraindicated to patients with a renal failure. In a type of lack of specialized researches among patients with impaired renal function, the recommendation about special correction of a dose cannot be provided. It is recommended to be careful at use of the drug Diklofenak-AKOS for patients with a slight and moderate renal failure.
Patients from the liver
of Diklofenak-AKOS broken by function it is contraindicated to patients with a liver failure. In a type of lack of specialized researches among patients from the liver broken by function, the recommendation about special correction of a dose cannot be provided. It is recommended to be careful at use of the drug Diklofenak-AKOS for patients with a slight and moderate abnormal liver function.
the Following undesirable effects include the phenomena connected with administration of the drug Diklofenak-AKOS, solution for injections and/or other dosage forms of diclofenac in the conditions of short-term and prolonged use.
Often (≥ 1/100, & lt, 1/10)
– a headache, dizziness
– nausea, vomiting, diarrhea, dyspepsia, an abdominal pain, a meteorism, hyporexia
– increase in level of transaminases
– a liquid delay, hypostases, arterial hypertension
– reaction in the place of an injection, pain in the place of an injection, hardening in the place of an injection
Infrequently (≥1/1.000 to & lt, 1/100)
– a myocardial infarction, heart failure, a cardiopalmus, a stethalgia
Seldom (≥ 1/10000, & lt, 1/1000)
– hypersensitivity, anaphylactic and pseudoanaphylactic reactions (including arterial hypotension and shock)
– asthma (including dispnoe)
– gastritis, gastrointestinal bleedings, vomiting with blood impurity, hemorrhagic diarrhea, a melena, ulcer of stomach or intestines (with bleeding or without it, perforation)
– hepatitis, jaundice, an abnormal liver function
– hypostasis, necrosis in the place of an injection
Is very rare (& lt, 1/10000)
– abscess in the place of an injection
– thrombocytopenia, a leukopenia, anemia (including hemolytic and aplastic anemia), an agranulocytosis
– a Quincke’s disease (including a face edema)
– a disorientation, a depression, insomnia, nightmares, irritability, mental disorders
– paresthesia, disturbance of memory, a spasm, uneasiness, a tremor, aseptic meningitis, disorder of sense of taste, an acute disorder of cerebral circulation
– a visual disturbance, illegibility of sight, a diplopia
– a ring in ears, a hearing disorder
– arterial hypertension, a vasculitis
– a pneumonitis
– colitis (including hemorrhagic colitis and exacerbation of ulcer colitis or Crohn’s disease), a constipation, stomatitis, a glossitis, disorders from a gullet, diafragmopodobny strictures of intestines, pancreatitis
– fulminantny hepatitis, gepatonekroz, a liver failure
– bullous dermatitis, eczema, an erythema, a multiformny erythema, Stephens-Johnson’s syndrome, a toxic epidermal necrolysis (Lyell’s disease), exfoliative dermatitis, an alopecia, reaction of photosensitivity, purple, purple of Genokha-Shenleyn, an itching
– an acute renal failure, a hamaturia, a proteinuria, a nephrotic syndrome, tubulointerstitsialny nephrite, renal papillary necrosis
Diclofenac, especially in high doses (150 mg/days) and at prolonged use, can increase risk of developing of an arterial thrombembolia (for example, a myocardial infarction or a stroke).
– the known hypersensitivity to active ingredient, sodium metabisulphite or to any other components of drug
– allergic reaction to other non-steroidal anti-inflammatory drugs (NPVP), for example, acetylsalicylic acid which can be expressed by asthma, urticaria, acute rhinitis or other allergic symptoms
– the III trimester of pregnancy and the period of a lactation
– active ulcer of stomach or intestines, bleeding or perforation
– a liver failure
– a renal failure
– heavy heart failure
– inflammatory bowel diseases (for example, Crohn’s disease or ulcer colitis)
– patients with high risk of developing postoperative bleedings, disturbances of a hemostasis and fibrillation, risk of hemopoietic disturbances or cerebrovascular bleedings
– treatment of postoperative pain after operation of coronary shunting (or uses of the cardiopulmonary bypass)
– children’s and teenage age up to 18 years
Powerful CYP2C9 inhibitors: It is recommended to be careful at joint prescribing of diclofenac with powerful CYP2C9 inhibitors (such as vorikonazol) which can lead to significant increase in peak of concentration in blood plasma and exposure of diclofenac at the expense of diclofenac metabolism inhibition.
Diklofenak-AKOS digoxin can increase concentration of lithium and digoxin in blood plasma. Monitoring of level of lithium and digoxin in blood serum is recommended.
Diuretics and antihypertensive drugs:
As well as for other NPVP, simultaneous use of diclofenac with diuretics or antihypertensive drugs (for example, beta-blockers, inhibitors of angiotensin-converting enzyme (APF)) can lead to decrease in their antihypertensive influence. Patients, especially elderly people, have to be under careful control of arterial blood pressure. Patients have to receive appropriate hydration, also monitoring of renal function after the beginning of the accompanying therapy and on a regular basis after it, especially concerning diuretics and APF inhibitors, owing to increase in risk of nephrotoxicity is recommended. The accompanying treatment by drugs of potassium can be connected with increase in level of potassium in blood serum that demands stay of patients under constant control.
Influence of NPVP on synthesis of prostaglandins in kidneys can increase nephrotoxicity of cyclosporine. Diclofenac should be applied in lower doses, than at patients who do not receive cyclosporine.
The drugs causing a hyperpotassemia
the Accompanying treatment by kaliysberegayushchy diuretics, cyclosporine takrolimusy or Trimethoprimum can increase serumal levels of potassium. It is necessary to control often potassium levels in blood serum.
Antibacterial agents – derivatives of a hinolon
Are available separate messages about development of spasms in patients, the receiving at the same time derivative hinolon and NPVP.
Other non-steroidal anti-inflammatory drugs (NPVP) and corticosteroids
Simultaneous system use of NPVP or corticosteroids with diclofenac can increase the frequency of emergence of the undesirable phenomena from digestive tract.
Anticoagulants and antitrombotichesky means
Exist separate messages about increase in risk of bleedings at the patients accepting at the same time Diklofenak-AKOS and anticoagulants. In case of such combination of medicines the careful and regular observation of patients is recommended.
The Selective Serotonin Reuptake Inhibitors (SSRI)
Co-administration of system NPVP and SIOZS can increase risk of gastrointestinal bleeding.
Perhaps simultaneous use of the drug Diklofenak-AKOS and antidiabetic drugs, at the same time the efficiency of the last does not change. Separate messages about development in such cases are known, to both a hypoglycemia, and a hyperglycemia that caused need of change of a dose of glucose-lowering drugs during drug Diklofenak-AKOS use.
Kolestipol and holestiramin
Simultaneous use of diclofenac and a kolestipol or holestiramin reduces diclofenac absorption approximately by 30% and 60%, respectively. The drugs should be taken at an interval of several hours.
The drugs stimulating enzymes which metabolize medicines
the Drugs stimulating enzymes, for example, rifampicin, carbamazepine, Phenytoinum, a St. John’s wort (Hypericum perforatum), etc. are theoretically capable to reduce concentration of diclofenac in plasma.
It is necessary to be careful when assigning NPVP less than in 24 hours prior to or after reception of a methotrexate as in such cases the concentration of a methotrexate in blood can increase and amplify its toxic action.
it is not necessary to mix the drug Diklofenak-AKOS solution which is contained in ampoules with solutions of other medicines for injections.
It is necessary to avoid use of the drug Diklofenak-AKOS with system NPVP, including selection inhibitors of cyclooxygenase-2, in a type of lack of any synergy advantage and a possibility of development of additional side effects.
It is necessary to be careful when prescribing drug to elderly people. With poor health and for patients with a low indicator of body weight it is recommended to apply the lowest effective doses to people of advanced age.
Asthma in the anamnesis
At patients with bronchial asthma, seasonal allergic rhinitis, a rhinedema (nasal polyps), with the chronic obstructive diseases of lungs or persistent infections of airways (which are especially connected with allergic, similar to rhinitises, symptoms) more often than others have reactions to NPVP similar to exacerbation of asthma, a Quincke’s edema or urticaria. Special measures (readiness for rendering emergency aid) are recommended to such patients. It also concerns patients with an allergy to other substances, for example, with skin reactions, an itching or urticaria.
Special cautions are recommended in case Diklofenak-AKOS is applied parenterally to patients with bronchial asthma as symptoms can become aggravated.
Influence on digestive system
As well as at use of other NPVP, when prescribing the drug Diklofenak-AKOS to patients with the symptoms demonstrating disturbances from the digestive system (DS) with presence of stomach ulcer or intestines, bleeding or perforation in the anamnesis, is obligatory medical observation and extra care. The risk of developing of bleeding in digestive tract increases with increase in a dose of drug at patients with an ulcer in the anamnesis, especially with complications in the form of bleeding or perforation, and at people of advanced age.
To reduce risk of toxic impact on PS at patients with an ulcer in the anamnesis, especially with complications in the form of bleeding or perforation and at people of advanced age, treatment is begun and supported by low effective doses.
For such patients and also the patients needing the accompanying use of the medicines containing low doses of acetylsalicylic acid or other medicines which presumably increase risk of undesirable impact on PS it is necessary to consider a question of use of combination therapy using protective equipment (for example, inhibitors of the proton pump or a mizoprostol).
Patients with gastrointestinal toxicity in the anamnesis, especially advanced age, have to report about any unusual abdominal symptoms (especially bleedings in PS). Cautions are also necessary for the patients receiving the accompanying drugs which can increase risk of developing an ulcer or bleeding, such as system corticosteroids, anticoagulants, antitrombotichesky means or selective serotonin reuptake inhibitors.
Diklofenak-AKOS it is necessary to appoint with care the patient in whose anamnesis there are inflammatory bowel diseases, such as Crohn’s disease or nonspecific ulcer colitis and to establish careful medical control and the appropriate preventive measures, in connection with potential aggravation.
Influence on a liver
Careful medical control is necessary in case Diklofenak-AKOS is appointed to patients with an abnormal liver function as the condition of such patients can become aggravated.
As well as at use of other NPVP, the level of one and more hepatic enzymes can increase. During long-term treatment, regular control of function of a liver is appointed the drug Diklofenak-AKOS (tablets or suppositories). If abnormal liver functions remain or worsen and also if the symptoms connected with the progressing liver diseases or other manifestations are observed (for example, an eosinophilia, rash), use of the drug Diklofenak-AKOS should be stopped. The course of diseases, such as hepatitis, can pass without prodromal symptoms.
The care is necessary in case Diklofenak-AKOS is applied at patients with a hepatic porphyria because of the probability of provocation of an attack.
Influence on kidneys
As at treatment of NPVP was reported about a delay of liquid and hypostasis, monitoring of renal function by the patient with dysfunction of heart or kidneys (including with a functional renal failure against the background of a hypovolemia, a nephrotic syndrome, a lupoid nephropathy and dekompensirovanny cirrhosis), arterial hypertension in the anamnesis is recommended, to the patients of advanced age, patients receiving therapy by diuretics or drugs which significantly influence function of kidneys, and to patients with significant decrease in extracellular volume of liquid for any reason, for example, to or after serious surgical intervention. The termination of therapy of NPVP usually leads to return to a state which preceded treatment.
Due to the use of NPVP, including Diklofenak-AKOS, it was very seldom reported about heavy, up to fatal, skin reactions, including exfoliative dermatitis, Stephens’s syndrome – Johnson and a toxic epidermal necrolysis. The highest risk of these reactions exists at the beginning of therapy, and development of these reactions is noted in most cases in the first month of treatment. Diklofenak-AKOS it is necessary to cancel at the first manifestations of skin rash, the centers of injury of a mucous membrane or any other manifestations of hypersensitivity.
As well as in a case with other NPVP, seldom or never with diclofenac there can be allergic reactions, including anaphylactic/anaphylactoid reactions, in the absence of former exposure to drug.
Influence on hematologic indicators
At prolonged use of drug, as well as other NPVP, is recommended blood test monitoring. As well as other NPVP, Diklofenak-AKOS can temporarily inhibit aggregation of thrombocytes. It is necessary to watch carefully patients with disturbances of a hemostasis.
Treatment of NPVP, including diclofenac, especially in high doses and during the long period, can be connected with small increase in risk of serious cardiovascular cases of thrombosis (including a myocardial infarction and a stroke). At the patients accepting NPVP, especially at patients with cardiovascular risk factors it is necessary to apply a minimal effective dose to minimizing of potential risk of collateral cardiovascular complications at the smallest admissible duration of treatment.
As a rule, therapy by the drug Diklofenak-AKOS is not recommended to patients with the established cardiovascular disease (stagnant heart failure, the established coronary heart disease, a peripheral arterial disease) or an uncontrollable hypertension. If necessary, Diklofenak-AKOS is appointed to patients with the established cardiovascular disease, an uncontrollable hypertension, or essential risk factors of a cardiovascular disease (hypertensia, a lipidemia, diabetes and smoking) only after thorough examination and only within daily doses ≤ 100 mg in case of therapy lasting over 4 weeks.
In a type of possible increase in risks from diclofenac from a cardiovascular system as a result of a dosage and duration of exposure, it is necessary to use a minimal effective dose during the minimum period. It is required to carry out periodically the repeated assessment of need for relief of symptoms and the response to therapy of the patient, in particular lasting therapy over 4 weeks.
Patients have to show vigilance concerning manifestations and symptoms of the heavy arteriotrombotichesky phenomena (for example, a stethalgia, short wind, weakness, the illegible speech) which can arise without the warning symptoms. Patients have to be instructed about need of urgent visit of the therapist for similar cases.
Can lead excipients of the drug Diklofenak-AKOS Metabisulfit natriya in solution for injections to the isolated heavy reaction of hypersensitivity and a bronchospasm.
Masking of manifestation of infectious diseases
of Diklofenak-AKOS, as well as other NPVP, thanks to the pharmakodinamichesky properties, can mask manifestations and symptoms of infectious diseases.
Pregnancy and the period of a lactation
of Diklofenak-AKOS should not be applied at the first two trimesters of pregnancy unless the potential advantage for mother exceeds possible risk for a fruit. Use during the third trimester of pregnancy is contraindicated owing to possible emergence of the phenomena of lack of reduction of a uterus and/or premature closing of ductus arteriosus.
Diclofenac gets into breast milk in a small amount. To avoid undesirable influence on the baby, Diklofenak-AKOS should not be applied during feeding by a breast. If treatment is extremely necessary, it is necessary to stop feeding by a breast and to transfer the child to artificial feeding.
of Diklofenak-AKOS can affect fertility of the woman. Drug is not recommended to the women planning pregnancy. The women having complications with fertilization or those which underwent inspection owing to an infertilnost have to stop drug Diklofenak-AKOS use.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
Patients at whom during the Diklofenak-AKOS drug treatment disorders of vision, dizziness, drowsiness or other disturbances are observed from the central nervous system have to abstain from control of motor transport and work with mechanisms.
Diklofenak-AKOS contains propylene glycol, in this regard can cause irritation of skin.
Symptoms: vomiting, gastrointestinal bleeding, diarrhea, dizziness, a ring in ears or spasms. In case of a serious poisoning the acute renal failure and damage of a liver is possible.
Treatment: the supporting measures and symptomatic treatment which are necessary for elimination of such complications as arterial hypotension, a renal failure, spasms, gastrointestinal disturbances and respiratory depression.
Special measures, such as artificial diuresis, dialysis or hemoperfusion, cannot guarantee removal of NPVP owing to their high linking with proteins of blood plasma and intensive metabolism.
A form of release and packing
On 3 ml of drug in ampoules with a capacity of 5 ml from neutral glass.
On 10 ampoules together with the instruction for medical use in the state and Russian languages and the scarificator ampoule place in a box of cardboard.
On 5 ampoules place in blister strip packaging from a film of the polyvinylchloride and printing aluminum foil varnished without foil.
1.2 blister strip packagings with the instruction for medical use in the state and Russian languages and the scarificator ampoule place in a pack from cardboard.
The scarificator ampoule in boxes and packs is not put in case of use of ampoules with a ring of a break or with a cut and a point.
To Store storage conditions in the place protected from light at a temperature not above 25 °C. Not to freeze.
To store out of children’s reach!
not to use a period of storage after an expiration date.
According to the prescription
JSC Sintez Producer 640008, Russia, Kurgan, Konstitutsii Avenue, 7
Ph./fax (3522) 48-16-89
the Owner of the registration certificate
of JSC Sintez, the Russian Federation
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products
of Decalog LLP,
050050, Republic of Kazakhstan, Almaty, Glazunov St., 41 A-1
ph. 2944221, ph. 8 7017315218
the Address of the organization responsible for post-registration observation of safety of medicine in the territory of the Republic of Kazakhstan
050050, Republic of Kazakhstan, Almaty, Glazunov St., 41 A-1
ph. 2944221, ph. 8 7017315218