Diclobrew

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

The active ingredient of the drug is diclofenac Na, a non-steroidal compound with strong anti-inflammatory, antipyretic, antirheumatic and analgesic activity. Suppression of PG biosynthesis processes is the main mechanism of the therapeutic effect of the drug. PG components are important participants in the development of pain, inflammation, and fever.

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Indications Diclobrew

It is used to treat the following disorders:

• degenerative or inflammatory types of rheumatism, osteoarthritis, rheumatoid arthritis, spondyloarthritis, non-articular rheumatism, Bechterew's disease and vertebral pain;
• gout in the active phase;
• colic of a biliary or renal nature;
• swelling and pain resulting from surgery or injury;
• severe migraine attacks.

The drug is administered via intravenous infusion to prevent or treat postoperative pain.

Release form

The medicinal component is released in the form of injection liquid, inside ampoules with a capacity of 3 ml. There are 5 such ampoules inside the tray. There is 1 tray in the pack.

Pharmacodynamics

During the treatment of pathologies of rheumatic origin, the analgesic and anti-inflammatory effect provides a clinical response in which the following manifestations of discomfort disappear: pain that appears during movement or at rest, and joint swelling and endogenous rigidity, and in addition, a significant improvement in activity is observed.

Diclofenac Na provides a pronounced analgesic effect on relatively severe and moderate pain of 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 relieve postoperative pain; the use of diclofenac Na significantly reduces the need for them.

Diclobru is required at the initial stage of therapy for pathologies of a rheumatic nature with degenerative and inflammatory activity, as well as pain arising from inflammation of non-rheumatic genesis.

Pharmacokinetics

Suction.

When 75 mg of the drug is given by injection, absorption begins immediately; mean plasma Cmax values of approximately 2.5 μg/mL are observed after approximately 20 minutes. The volume absorbed may be linearly related to the dose size.

When using 75 mg diclofenac via infusion, after 2 hours the average Cmax values are approximately 1.9 μg/ml. With shorter infusions the Cmax level in the blood plasma increases, and with long procedures the values are proportional to the infusion values after 3-4 hours. During injections or the use of gastro-resistant tablets the plasma values decrease rapidly after the Cmax level has developed.

Bioavailability.

The AUC values of the drug after intravenous or intramuscular administration are approximately twice the level after oral use, because in the latter case about half of the active element undergoes the first intrahepatic passage.

Pharmacokinetic characteristics do not change with repeated use. If the required intervals between drug administrations are observed, accumulation does not develop.

Distribution processes.

The synthesis of the drug with whey protein is 99.7% (mostly with albumin – 99.4%). The distribution volume indicators are in the range of 0.12-0.17 l/kg.

The active component of the drug penetrates into the synovium, reaching Cmax values there after 2-4 hours from the moment the plasma Cmax level is reached.

The half-life from synovium is assumed to be 3-6 hours. After 2 hours from the moment of obtaining plasma Cmax inside synovium, these values exceed plasma levels and remain high for the next 12 hours.

Exchange processes.

Diclofenac metabolism processes are partly realized through glucuronidation of the intact molecule, but mainly through single and multiple 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 is significantly less intense than that of diclofenac.

Excretion.

The overall plasma clearance values of the drug are 263±56 ml per minute (mean ± SD). The terminal plasma half-life is 1-2 hours. The four metabolic components (both active) also have a short plasma half-life, in the range of 1-3 hours. One metabolic element has a much longer blood half-life, but has almost no therapeutic activity.

About 60% of the dose used is excreted in the urine in the form of conjugates combined with glucuronic acid formed from the intact molecule, as well as in the form of metabolic components, most of which are transformed into glucuronide-type conjugates. Less than 1% of the substance is excreted unchanged. The remainder of the dose is eliminated as metabolic elements along with feces and bile.

Dosing and administration

The medication can be used for a maximum of 2 days. If continued therapy is required, other forms of diclofenac should be used. The medication is prescribed in the most effective doses for a short period of time, taking into account the patient's clinical picture.

The ampoules of the medicine can be used only once, the medicinal liquid should be administered immediately after opening the ampoule. Unused remains should be disposed of.

Administration by injection.

To prevent damage to nerves and other tissues in the injection area, follow the instructions below.

A single dose is often 75 mg per day (1 ampoule); it is administered by injection, deep into the outer upper quadrant of the gluteal muscle. In severe disorders (e.g. colic), the daily dosage may be increased to 2 injections of 75 mg; in this case, an interval of several hours must be observed between them (1 injection in each buttock). An alternative scheme may also be used - 75 mg from an ampoule in combination with other forms of diclofenac Na, with a total maximum permissible daily dose of 0.15 g.

During a migraine attack, it is recommended to initially administer 75 mg of the drug (1 ampoule).

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

There is no available information regarding the use of the drug for migraine attacks lasting longer than 1 day.

Administration of intravenous infusions

The medication is prohibited to be administered via bolus injection.

Before the procedure, the medicine is dissolved in 0.9% NaCl or 5% glucose liquid (0.1-0.5 l), buffered with injection sodium bicarbonate (8.4% liquid by 0.5 ml or 4.2% liquid by 1 ml or other required volume), taken from a freshly opened container. Only transparent liquids are allowed to be used. If it contains sediment or crystals, it is not used for infusion.

There are 2 alternative dosage regimens that can be used:

• therapy of severe or moderate postoperative pain – 75 mg of the substance is administered continuously for 0.5-2 hours. If necessary, the therapy can be repeated after 4-6 hours, but the dosage should not exceed 0.15 g per day;
• prevention of postoperative pain - 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 to achieve a maximum daily dosage of 0.15 g.

Elderly people.

Although the pharmacokinetic parameters of the drug do not change too much in elderly people, they need to use NSAIDs very carefully, because they have a higher tendency to develop negative symptoms. For example, weakened elderly people or people with low weight need to use the minimum effective doses. At the same time, during NSAID therapy, such patients need to be examined for bleeding inside the gastrointestinal tract.

It is recommended to take no more than 0.15 g of Diclobru per day.

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Use Diclobrew during pregnancy

In the 1st and 2nd trimesters, the medication may be prescribed only in situations where the probable benefit to the woman is more expected than the risks of complications for the fetus; only minimal effective dosages may 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 may suppress uterine contractility, and the fetus may experience premature closure of the arterial duct).

Inhibition of PG binding may have a negative effect on the course of pregnancy or the development of the embryo/fetus. Epidemiological testing has shown that there is an increased risk of miscarriage or heart defects after the introduction of PG synthesis inhibitors early in pregnancy. The absolute risk of cardiovascular abnormalities has increased from less than 1% to 1.5%.

There is a possibility that this risk increases with increasing dosage and duration of therapy. In animals, the use of a PG binding inhibitor has been shown to increase post- and preimplantation losses and embryonic or fetal mortality.

In addition, animals that were administered inhibitors of PG binding processes during organogenesis showed an increased frequency of various developmental abnormalities (also associated with the work of the cardiovascular system). When using diclofenac in women planning to conceive, or in the first trimester, the dose should be as low as possible, and the duration of the course should be as short as possible.

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

• toxicity affecting the lungs and heart (with pulmonary hypertension and too early closure of the arterial pathway);
• renal dysfunction, which may progress to failure, combined with oligohydramnios.

Effects in late pregnancy and on the woman and newborn:

• antiplatelet activity may develop, observed even at extremely low doses, and the bleeding period may be prolonged;
• slowing of uterine contractions, which results in prolongation or delay of the labor process.

Like other NSAIDs, diclofenac in small portions can pass into breast milk. Therefore, to avoid negative effects on the child, the drug is not used during breastfeeding. If there is a strong need for therapy, you should stop breastfeeding.

Contraindications

Main contraindications:

• severe intolerance associated with the active ingredient, sodium metabisulfite or other components of the drug;
• like other NSAIDs, diclofenac should not be prescribed to people for whom the use of aspirin, ibuprofen and other NSAIDs causes the development of Quincke's edema, bronchial asthma, acute rhinitis or urticaria;
• history of perforations or bleeding in the gastrointestinal tract caused by previous therapy with NSAIDs;
• bleeding or ulcer in the active phase, or bleeding and recurrent ulcer in the anamnesis (2+ separate cases with diagnosis of bleeding or ulcer);
• inflammations affecting the intestinal area (for example, ulcerative colitis or regional enteritis);
• renal or hepatic failure;
• high probability of postoperative bleeding, hemostasis disorders, blood clotting, hematopoietic manifestations or cerebrovascular bleeding;
• CHF (NYHA II-IV);
• IHD in people with angina pectoris who have had a myocardial infarction;
• cerebrovascular pathologies in individuals who have previously suffered a stroke or had TIA attacks;
• diseases affecting peripheral arteries;
• elimination of peripheral pain that occurs in the case of coronary artery bypass grafting (or as a result of the use of artificial cardiac output).

Contraindications for intravenous administration:

• combination with anticoagulants or NSAIDs (also with low doses of heparin);
• the presence in the anamnesis of a hemorrhagic nature of diathesis, as well as diagnosed or suspected cerebrovascular bleeding (along with this, the presence in the anamnesis);
• operations in which there is a high risk of bleeding;
• history of asthma;
• severe or moderate renal impairment (serum creatinine levels >160 μmol/L);
• dehydration or hypovolemia caused by any factors.

Side effects Diclobrew

Side effects include:

• lesions of the lymph and hematopoietic system: leukopenia or thrombocytopenia appear sporadically, as well as agranulocytosis and anemia (aplastic or hemolytic variety);
• immune disorders: intolerance, pseudoanaphylactic or anaphylactic symptoms (including shock and hypotension) are occasionally observed. Quincke's edema (also facial swelling) is observed sporadically;
• mental health problems: isolated cases of depression, irritability, disorientation, nightmares, insomnia and mental disorders;
• disorders of the nervous system: dizziness or headaches are often observed. Occasionally, severe fatigue or drowsiness occurs. Sporadic seizures, memory disorders, paresthesia, tremor, taste disturbance, anxiety, stroke and aseptic meningitis occur. Hallucinations, general malaise, confusion and sensory disorders may develop;
• visual disturbances: occasional blurred vision or visual disturbances, as well as diplopia. Neuritis affecting the optic nerves is possible;
• lesions of the auditory organs and labyrinth: vertigo is often observed. Hearing disorders or tinnitus occur sporadically;
• manifestations affecting the heart: occasional pain in the sternum area, myocardial infarction, palpitations and heart failure;
• vascular dysfunction: vasculitis develops occasionally, blood pressure increases or decreases;
• thoracic, respiratory and mediastinal disorders: asthma (also with dyspnea) occasionally occurs. Pneumonitis is observed sporadically;
• pathologies affecting the digestive system: diarrhea, bloating, vomiting, abdominal pain, nausea, anorexia and dyspepsia often occur. Melena, gastritis, bloody vomiting, hemorrhagic diarrhea, gastritis, intestinal bleeding, and ulcers in the gastrointestinal tract, accompanied (or not) by bleeding or perforation (sometimes leading to death, especially in the elderly), are rare. Glossitis, colitis (also hemorrhagic variety, ulcerative in the active phase or granulomatous enteritis), stomatitis (also ulcerative form), obstipation, pancreatitis, membranous intestinal strictures and disorders associated with the esophagus are observed isolatedly;
• disorders associated with hepatobiliary function: an increase in transaminase values is often noted. Rarely, liver dysfunction, jaundice or hepatitis develop. Hepatonecrosis, hyperacute hepatitis and liver failure occur sporadically;
• lesions of the subcutaneous layer and epidermis: rashes often occur. Urticaria develops occasionally. Eczema, SJS, erythema multiforme and its other varieties, bullous rashes, exfoliative dermatitis, TEN, photosensitivity, alopecia, itching and purpura (also of allergic origin) are observed sporadically;
• urinary and renal dysfunction: hematuria, acute renal failure, necrotic papillitis, nephrotic syndrome, proteinuria and tubulointerstitial nephritis appear occasionally;
• Systemic disorders and manifestations at the injection site: symptoms at the injection site, hardening and pain are often observed. Occasionally, necrosis and swelling are observed at the injection site. Abscesses occur sporadically;
• lesions affecting the mammary glands and reproductive organs: impotence occasionally occurs.

Epidemiological data and information obtained from clinical trials demonstrate an increased likelihood of developing complications of a thrombotic nature (e.g. 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, one can expect the following symptoms: epigastric pain, diarrhea, nausea, gastrointestinal bleeding and vomiting. In addition, headaches, agitation, drowsiness, convulsions, dizziness, coma, disorientation, loss of consciousness and tinnitus are possible. In case of severe intoxication, liver damage or acute renal failure may occur.

Activated carbon may be taken within 60 minutes of the administration of a potentially toxic volume of the drug. However, gastric lavage may also be performed during this period. If prolonged or frequent convulsions are observed, intravenous diazepam is required. Other treatment measures may be prescribed in accordance with the clinical picture. Symptomatic procedures are also performed.

Interactions with other drugs

Lithium agents.

Combination with diclofenac may cause an increase in plasma lithium levels, so serum lithium levels should be monitored during such treatment.

Digoxin.

Combining Diclobru with digoxin increases the plasma levels of the latter, so it is necessary to monitor the serum level of digoxin during therapy.

Antihypertensive and diuretic drugs.

As with other NSAIDs, when diclofenac is combined with antihypertensive or diuretic drugs (for example, ACE inhibitors or β-blockers), their hypotensive activity may be weakened due to slower binding of vasodilating prostaglandins. Therefore, such a combination should be used very carefully, especially in the elderly - their blood pressure indicators should be closely monitored. Patients should be provided with the required hydration, and at the same time, kidney function should be monitored (also after the end of treatment), especially with respect to the combination of diuretics and ACE inhibitors, because this increases the likelihood of developing nephrotoxic properties.

Substances that may cause hyperkalemia.

Combination with cyclosporine, potassium-sparing diuretics, trimethoprim or tacrolimus may provoke an increase in serum potassium levels, which is why the patient's condition should be constantly monitored.

Other NSAIDs, including corticosteroids and selective COX-2 inhibitors.

Combination of the drug with other systemic NSAIDs or GCS may increase the risk of ulcers or bleeding in the gastrointestinal tract. It is necessary to avoid the simultaneous use of 2+ NSAIDs.

Antithrombotic drugs and anticoagulants.

Such therapy should be carried out with great caution, because such a combination increases the likelihood of bleeding. Although clinical tests have not revealed the effect of diclofenac on the effectiveness of anticoagulants, there is some information confirming an increased likelihood of bleeding in individuals using diclofenac together with anticoagulants. Such patients should be closely monitored.

SSRI substances.

The combined use of systemic NSAIDs with SSRIs may increase the risk of bleeding within the digestive system.

Hypoglycemic drugs.

Diclofenac can be used in combination with antidiabetic drugs for oral administration without affecting their medicinal effectiveness. However, there is data on the development of a hyper- or hypoglycemic effect, in which case, during therapy with diclofenac, it is necessary to change the dose of the hypoglycemic substance. In such conditions, it is necessary to monitor blood sugar levels - as a precaution.

Cholestyramine with colestipol.

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

Medicines that stimulate the activity of enzymes that metabolize drugs.

Enzyme-stimulating substances, including carbamazepine, St. John's wort, and rifampicin with phenytoin, may in theory decrease plasma levels of diclofenac.

Methotrexate.

If NSAIDs are used less than 24 hours before or after methotrexate, caution should be exercised because methotrexate blood levels may increase, thereby increasing the toxic properties of this drug.

The drug can inhibit the clearance of methotrexate inside the renal tubules, causing its levels to increase. There is information about the development of severe toxicity when using NSAIDs with methotrexate during a single 24-hour period. With such an interaction, there is an accumulation of methotrexate associated with a disorder of renal excretory function due to the action of NSAIDs.

Tacrolimus with cyclosporine.

Like other NSAIDs, diclofenac can potentiate the nephrotoxic activity of cyclosporine by affecting renal PG. A similar risk occurs with therapy using tacrolimus. Because of this, it should be used in lower doses than in people who do not use cyclosporine.

Quinolones of antibacterial nature.

There are isolated reports of seizures that may develop as a result of combining NSAIDs with quinolones. They may occur in individuals with or without a history of seizures or epilepsy. Therefore, quinolones should be used with extreme caution in individuals already taking NSAIDs.

Phenytoin.

The administration of phenytoin together with the drug requires constant monitoring of plasma parameters of the former, because there is a risk of increasing the level of phenytoin exposure.

Cardiac glycosides.

The combination of CG with NSAIDs may potentiate cardiac failure, increase plasma glycoside levels and decrease the rate of CF.

Mifepristone.

NSAIDs should not be administered within 8-12 days of using mifepristone, as they may weaken its medicinal properties.

Potent agents that inhibit CYP2C9 activity.

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

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Storage conditions

Diclobru should be stored in a place closed to small children and sunlight. Temperature – no more than 25°C.

Shelf life

Diclobru is approved for use for a period of 36 months from the date of manufacture of the therapeutic agent.

Application for children

Diclobru injection solutions should not be prescribed in pediatrics.

Analogues

The analogs of the drug are Almiral, Diclac with Voltaren, as well as Divido and Diclo-Denk 100 Rectal.

Reviews

Diclobru receives good reviews from patients. The comments indicate that the medicine quickly eliminates even the most severe and sharp pains, effectively acting in cases where other means do not help. It is only necessary to take into account that the medicine cannot be used for a long time, because it is a potent substance.