Diclobur

Diclobru is a drug from the NSAID subgroup, a derivative of ethanoic acid.

The active element of the drug is the substance Diclofenac Na, a compound of the non-steroid type, which has a strong anti-inflammatory, antipyretic, antirheumatic and analgesic activity. Suppression of PG biosynthesis processes is the main mechanism of therapeutic effect of drugs. GHG components are important participants in the development of pain, inflammation, and fever.

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Indications Diclobur

Used for the treatment of such disorders:

• degenerative or inflammatory types of rheumatism, osteoarthritis, rheumatoid arthritis, spondylitis, non-articular rheumatism, ankylosing spondylitis, and vertebral pain;
• gout in the active phase;
• biliary or renal colic;
• swelling and pain resulting from surgery or injury;
• severe migraine attacks.

Via IV infusion, the drug is injected to prevent or treat postoperative pain.

Release form

The release of the drug component is made in the form of injection fluid, inside an ampoule with a capacity of 3 ml. Inside the pallet contains 5 such ampoules. In a pack - 1 pallet.

Pharmacodynamics

During treatment, pathologies with a rheumatic nature, analgesic and anti-inflammatory effects provide a clinical response in which the following symptoms of discomfort disappear: pain that occurs during movement or at rest, and articular swelling and endogenous rigidity, and in addition there is a significant improvement in activity.

Diclofenac Na provides a pronounced analgesic effect on relatively severe and moderate pain, having a non-rheumatic etiology, over a 15–30-minute period. In addition, the drug is effective in the development of migraine attacks.

The drug is used in combination with opioid analgesics used to eliminate postoperative pain; the use of diclofenac Na significantly reduces the need for them.

Diclobru is required at the initial stage of therapy of having degenerative and inflammatory activity of rheumatic pathology, as well as pain resulting from inflammation of non-rheumatic genesis.

Pharmacokinetics

Suction.

When using 75 mg of the drug via injection, absorption begins immediately; mean plasma Cmax values of approximately 2.5 μg / ml are noted after about 20 minutes. Absorbent volume may be linearly dependent on the size of the portion.

When using 75 mg of diclofenac via infusion, after 2 hours, the average Cmax values are approximately 1.9 µg / ml. With shorter infusions, the Cmax level inside the blood plasma rises, while with longer procedures, indicators are observed that are proportional to the values of the infusion after 3-4 hours. During injections or the use of gastro-resistant tablets, plasma values decrease rapidly after the development of a Cmax level.

Bioavailability.

The AUC values of the drug for i / v or i / m administration are approximately twice the level after oral use, because in the latter case about half of the active element undergoes the 1st intrahepatic passage.

Pharmacokinetic characteristics do not change with repeated use. In the case of compliance with the required intervals between injections of drugs, cumulation does not develop.

Distribution processes.

Synthesis of the drug with whey protein is equal to 99.7% (most of the albumin - 99.4%). Distribution volume indicators - in the range of 0.12-0.17 l / kg.

The active component of the drug passes inside the synovium, reaching Cmax values there after 2-4 hours from the moment of obtaining the plasma level Cmax.

The imaginary term half-life of synovia is 3-6 hours. After 2 hours from the moment of receiving plasma Cmax inside synovia, these values exceed the plasma level, and remain high for the next 12 hours.

Exchange processes.

Diclofenac metabolism processes are partly realized through the glucuronidation of an intact molecule, but mainly through 1-time and reusable methoxylation and hydroxylation, which result in the formation of phenolic metabolic elements, most of which are transformed into a glucuronide conjugate. Two phenolic metabolic components have bioactivity, but their effect has a much lower intensity than that of diclofenac.

Excretion.

The total plasma clearance of the drug is 263 ± 56 ml per minute (mean ± SD). The terminal half-life of blood plasma is 1-2 hours. Four metabolic components (also both active) also have a short term plasma half-life - in the range of 1-3 hours. One metabolic element has a much longer term half-life from the blood, but it almost does not possess therapeutic activity.

About 60% of the used dosage is excreted in the urine in the form of conjugates combined with glucuronic acid, formed from the intact molecule, and also in the form of metabolic components, most of which are transformed into glucuronide-type conjugates. Less than 1% of the substance excreted unchanged. Portion residues are eliminated under the guise of metabolic elements along with feces and bile.

Dosing and administration

The medication can be used for a maximum of 2 days. If continuation of therapy is required, it is necessary to use other forms of diclofenac release. The drug is prescribed in the most effective portions over a short period of time, taking into account the clinical picture of the patient.

Ampoules of medication can only be used 1-fold, it is necessary to inject medicinal liquid immediately after opening the ampoule. Unused residues must be disposed of.

Introduction through injection.

To prevent damage to the nerve and other tissues in the area of the injection, it is required to follow the instructions described below.

A single portion often equals 75 mg per day (1 ampoule); it is administered through an injection, deep inside the outer upper quadrant of the muscles of the buttocks. In severe disorders (for example, colic), the daily dosage is allowed to increase to 2 injections of 75 mg; at the same time between them it is required to observe a gap of several hours (1 injection in the region of each buttock). An alternative scheme can also be used - 75 mg from an ampoule in combination with other forms of diclofenac Na, with a total maximum allowable daily portion of 0.15 g.

In case of a migraine attack, it is recommended to inject 75 mg of medication for the beginning (1 ampoule).

During the day (first) total portion can be no more than 175 mg.

Available information on the use of medication for migraine attacks for a period longer than 1 day is not available.

Intravenous Infusion

The drug is forbidden to use through a bolus injection.

Before the procedure, the drug is dissolved in 0.9% NaCl or 5% glucose liquid (0.1-0.5 l) buffered with injection sodium bicarbonate (8.4% liquid 0.5 ml or 4, 2% liquid (1 ml each or other required volume) taken from a freshly opened container. Only transparent liquids are allowed. In the presence of sediment or crystals in it, it is not used for infusion.

You can use 2 alternative dosing regimens:

• treatment of severe or moderate post-operative pain - 75 mg of the substance are administered continuously for 0.5-2 hours. When needed, the therapy is allowed to repeat after 4-6 hours, but the dosage should be no more than 0.15 g per day;
• warning of post-treatment pains - after 15-60 minutes from the moment of the operation, a loading dose of 25-50 mg is administered, and then a continuous infusion of approximately 5 mg / hour is used with a maximum daily dosage of 0.15 g.

Elderly people.

Given that the elderly pharmacokinetic parameters of the drug do not change too much, they need to be very careful with the use of NSAIDs, because they have a higher tendency to the appearance of negative signs. For example, weakened older people or people with low weight are required to use the minimum effective portions. At the same time, during the treatment of NSAIDs, such patients should be examined for bleeding inside the gastrointestinal tract.

During the day it is recommended to introduce no more than 0.15 g Diklobryu.

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Use Diclobur during pregnancy

In the 1st and 2nd trimesters, the drug is allowed to be prescribed only in situations where the likely benefit for the woman is more expected than the risks of complications for the fetus; only minimal effective dosages can be used, and the duration of therapy should be as short as possible. Like other NSAIDs, Diclobru cannot be administered in the 3rd trimester (because it can suppress the contractile activity of the uterus, and in the fetus it may be too early to close the arterial duct).

Slowing of GHG binding can have a negative impact on the course of pregnancy or the development of the embryo / fetus. During epidemiological testing, it was found that there is an increased likelihood of miscarriages or the appearance of heart defects after the introduction of agents that slow down the synthesis of GHGs at an early stage of gestation. Absolute risk indicators for the occurrence of cardiovascular abnormalities increased from below 1% to 1.5%.

It is likely that this risk increases with increasing dosage and duration of therapy. It has been established that in animals with the use of a GHG binding inhibitor, post- and preimplantation losses and mortality of the embryo or fetus increase.

In addition, in animals that were injected with inhibitors of the processes of PG binding during organogenesis, there was an increased frequency of various developmental abnormalities (also associated with CVS). When using diclofenac in women planning to conceive, or in the 1st trimester, the portion should be as low as possible, and the duration of the course as short as possible.

In the 3rd trimester, any medications that slow down the binding of GHGs can affect the fetus in this way:

• pulmonary and heart toxicity (with pulmonary hypertension and too early closure of the arterial pathway);
• disorder of renal work, which can reach the development of insufficiency, combined with oligohydramnios.

Effects on the late stage of gestation, as well as on the woman and the newborn:

• antiaggregant activity may develop, which is observed even at extremely low portions, and prolong the period of bleeding;
• the slowing of uterine contractions, because of which there is a prolongation or delay of the labor process.

Like other NSAIDs, diclofenac in small portions is able to pass inside the mother's milk. Therefore, in order to avoid a negative impact on the child, the medicine is not used during breastfeeding. With a strong need for therapy, breastfeeding should be abandoned.

Contraindications

The main contraindications:

• severe intolerance associated with the active element, sodium metabisulfite, or other elements of the drug;
• like other NSAIDs, diclofenac should not be prescribed to people who use aspirin, ibuprofen and other NSAIDs causes Quincke edema, BA, an acute form of rhinitis or urticaria;
• the presence in the history of perforations or bleeding in the area of the gastrointestinal tract, caused by previous therapy with NSAIDs;
• bleeding or an ulcer in the active phase, or bleeding and recurrent ulcer, available in history (2+ individual cases with the diagnosis of bleeding or ulcers);
• inflammations affecting the intestinal area (for example, ulcerative colitis or regional enteritis);
• kidney or liver failure;
• high probability of postoperative bleeding, disorders of hemostasis, blood coagulation, hematopoietic manifestations or cerebrovascular bleeding;
• ZNN (NYHA II-IV);
• Coronary artery disease in people with angina who suffered myocardial infarction;
• cerebrovascular pathology in persons who have previously had a stroke, or who have had TIA attacks;
• diseases affecting peripheral arteries;
• elimination of peripheral pains appearing in the case of coronary artery bypass surgery (or as a result of AIC).

Contraindications for on / in the introduction:

• combination with anticoagulants or NSAIDs (also with low portions of heparin);
• the presence of diathesis in the history of hemorrhagic nature, as well as cerebrovascular character diagnosed or suspected of bleeding (along with this, and a history of);
• surgeries for which there is a high probability of bleeding;
• history of asthma;
• severe or moderate kidney dysfunction (serum creatinine levels are> 160 μmol / l);
• dehydration or hypovolemia caused by any factors.

Side effects Diclobur

Among the side effects:

• lesions of the lymph and hematopoietic system: leuko- or thrombocytopenia appears singly, as well as agranulocytosis and anemia (aplastic or hemolytic species);
• immune disorders: rarely intolerance, pseudo-anaphylactic or anaphylactic symptoms (among them, shock and hypotension). Quincke edema is singled out solely (also facial edema);
• mental problems: depression, irritability, disorientation, nightmares, insomnia and mental disorders are rarely observed;
• disorders in the work of the National Assembly: dizziness or headaches are often noted. Occasionally severe fatigue or drowsiness occurs. Seizures of spasms, memory disorders, paresthesias, tremor, gustatory disturbance, anxiety, stroke, and aseptic type of meningitis appear singly. Perhaps the development of hallucinations, malaise, confusion and sensitivity disorders;
• visual disturbances: visual misting or visual disturbances, as well as diplopia, are rarely observed. Possible neuritis, affecting the optic nerves;
• lesions of the auditory organs and the labyrinth: vertigo is often marked. Hearing disorders or ear ringing occur sporadically;
• manifestations affecting the heart: a single pain in the sternum area, myocardial infarction, palpitations and heart failure;
• impaired vascular function: single vasculitis develops, the blood pressure index rises or decreases;
• thoracic, respiratory and mediastinal disorders: BA occasionally occurs (also with dyspnea). Pneumonitis is observed individually;
• pathologies affecting the digestive activity: often diarrhea, bloating, vomiting, abdominal pain, and also nausea, anorexia and dyspepsia. Occasionally, melena, gastritis, hematemesis, hemorrhagic diarrhea, gastritis, bleeding inside the intestines, and ulcers in the gastrointestinal zone, accompanied (or not) by bleeding or perforation (sometimes lead to death, especially in elderly people) occur rarely. Glossitis, colitis (also a hemorrhagic variety, ulcerative in the active phase, or granulomatous enteritis), stomatitis (also ulcerative form), constipation, pancreatitis, intestinal membrane strictures and disorders related to the esophagus;
• disorders associated with hepatobiliary function: an increase in transaminase values is often noted. Occasionally, a liver disorder, jaundice, or hepatitis develops. Hepatonecrosis, ultrafast hepatitis and liver failure are sporadic;
• lesions of the subcutaneous layer and epidermis: rashes often occur. Occasionally develops urticaria. Eczema, SJS, erythema polyforma and its other varieties, bullous rash, exfoliative dermatitis, TEN, photosensitization, alopecia, pruritus and purpura (also of an allergic nature) are rarely observed;
• disorders of the urinary and renal activities: hematuria, acute renal failure, necrotizing papillitis, nephrotic syndrome, proteinuria and tubulo-interstitial nephritis;
• systemic disorders and manifestations in the injection area: symptoms at the injection site are often observed, hardening and pain. Occasionally marked necrosis and puffiness in the area of injection. Absorbs occur sporadically;
• lesions affecting the mammary glands and reproductive organs: impotence rarely appears.

Epidemiological information and information obtained from clinical tests demonstrate an increased likelihood of thrombotic complications (for example, stroke or myocardial infarction) caused by the use of diclofenac, for example, in large therapeutic doses (0.15 g per day) and in the case of prolonged administration.

Overdose

In case of diclofenac poisoning, symptoms such as epigastric pain, diarrhea, nausea, gastrointestinal bleeding and vomiting can be expected. In addition, headaches, agitation, drowsiness, convulsions, dizziness, coma, disorientation, loss of consciousness and ear ringing are possible. In severe intoxication, hepatic impairment or acute renal failure may occur.

For 60 minutes after the introduction of the potentially toxic amount of the drug, you can take activated charcoal. However, gastric lavage can also be performed in this gap. If there are prolonged or frequent seizures, it is required in / in the use of diazepam. In accordance with the clinical picture, other therapeutic measures may be prescribed. Symptomatic procedures are also performed.

Interactions with other drugs

Lithium products.

Combination with diclofenac may cause an increase in plasma indicators of lithium, therefore, with this treatment, serum values of lithium should be monitored.

Digoxin.

Combining Diclobe with digoxin increases the plasma values of the latter, therefore during therapy it is required to monitor the serum level of digoxin.

Antihypertensive and diuretic drugs.

As with other NSAIDs, the combination of diclofenac and hypotensive or diuretic drugs (for example, ACE inhibitors or β-blockers) may weaken their hypotensive activity due to slower binding of vasodilating prostaglandins. Therefore, this combination is used very carefully, especially for older people - they need to carefully monitor blood pressure indicators. Patients need to ensure the required hydration, and at the same time monitor the work of the kidneys (also after the end of treatment), especially regarding the combination of diuretics and ACE inhibitors, because this increases the likelihood of nephrotoxic properties.

Substances that can cause hyperkalemia.

A combination with cyclosporine, a diuretic of a potassium-sparing nature, trimethoprim or tacrolimus can provoke an increase in serum potassium indicators, due to which the condition of patients must be constantly monitored.

Other NSAIDs, including GCS and selective inhibitors of COX-2 activity.

The combination of medication with other systemic NSAIDs or GCS can lead to an increase in the likelihood of ulceration or bleeding inside the gastrointestinal tract. It is necessary to abandon the simultaneous use of 2+ NSAIDs.

Antithrombotic drugs and anticoagulants.

It is required to carry out such therapy with great caution, because such a combination increases the likelihood of bleeding. Although clinical tests did not reveal the effects of diclofenac on the effectiveness of anticoagulants, there is some information confirming the increased likelihood of bleeding in individuals using diclofenac together with anticoagulants. Such patients should be carefully monitored.

Substances SSRIs.

Combined use of systemic NSAIDs with SSRIs may increase the likelihood of bleeding inside the digestive system.

Hypoglycemic drugs.

Diclofenac can be used in combination with antidiabetic drugs for oral administration without affecting their drug efficacy. But there is evidence of the development of a hyper- or hypoglycemic effect, in which, during therapy with diclofenac, a change in the portion of the hypoglycemic substance is necessary. In such conditions, it is necessary to monitor blood sugar indicators - as a precaution.

Cholestyramine with colestipol.

The combination of Diclobrus with cholestyramine or colestipol can lead to a decrease or delay in the absorption of diclofenac. Therefore, the drug should be applied at least 60 minutes before or 4 to 6 hours after the administration of cholestyramine or colestipol.

Medicines that stimulate the activity of enzymes that metabolize drugs.

Stimulating the enzyme activity of substances, among which carbamazepine, St. John's wort, and rifampicin with phenytoin, in theory, can lower the plasma indicators of diclofenac.

Methotrexate.

In the case of the use of NSAIDs less than 24 hours before or after the use of methotrexate, care must be taken, because the blood indicators of the latter can increase, thereby increasing the toxic properties of this tool.

The drug can inhibit the clearance of methotrexate inside the tubules of the kidneys, because of which its indicators are growing. There is information about the development of strong toxicity when using NSAIDs with methotrexate during one 24-hour period. With this interaction, methotrexate is cumulated due to a disorder of the renal excretory function due to the action of NSAIDs.

Tacrolimus with ciclosporin.

Like other NSAIDs, diclofenac is able to potentiate the nephrotoxic activity of cyclosporine, affecting renal PG. A similar risk occurs with tacrolimus therapy. Because of this, it should be used in lower portions than those who do not use cyclosporine.

Antibacterial quinolones.

There is some information about seizures that may develop as a result of a combination of NSAIDs with quinolones. They can occur in individuals with a history of seizures or epilepsy, and in individuals without such anamnesis. Therefore, it is necessary to use quinolones with extreme caution in people who already use NSAIDs.

Phenytoin.

The introduction of phenytoin together with the drug requires continuous monitoring of plasma parameters of the first, because there is a risk of increasing the level of exposure to phenytoin.

Cardiac glycosides.

The combination of SG with NSAIDs can potentiate the failure of cardiac function, increase plasma glycoside indices, and decrease the rate of CF.

Mifepriston.

Substances NSAIDs can not be prescribed for 8-12 days from the time of use of mifepristone, because they can weaken its medical properties.

Potent agents that slow down the activity of CYP2C9.

Combining such drugs (for example, voriconazole) with diclofenac can significantly increase the plasma values of Cmax and AUC of the latter, which leads to the suppression of its metabolic processes.

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Storage conditions

Diklobryu must be kept in a closed place from small children and sunlight. Temperature - no more than 25 ° C.

Shelf life

Diclobru is allowed to apply for a 36-month term since the production of the therapeutic agent.

Application for children

Diclobru injection solutions can not be prescribed in pediatrics.

Analogs

Analogues of the drug are the substances Almiral, Diklak with Voltaren, as well as Divido and Diklo-Denk 100 Rectal.

Reviews

Diklobru receives good reviews from patients. The comments indicate that the medicine quickly eliminates even the strongest and sharpest pains, effectively acting in cases where other means fail. It is only necessary to take into account that the drug can not be used for a long time, because it is a potent substance.