Bioran

Bioran is a medicine from the NSAID subgroup. Its active component is diclofenac Na (a non-steroidal element with strong anti-inflammatory, antipyretic, and analgesic effects).

The main principle of diclofenac's influence is the slowing down of PG biosynthesis (these elements are important participants in the processes of pain, inflammation, and fever development). [ 1 ]

During rheumatic lesions, the analgesic and anti-inflammatory effects of the drug cause a significant reduction in the intensity of pain that occurs during movement or at rest, stiffness in the morning and joint swelling, and in addition, improve the functioning of the joints.

Indications Bioran

It is used for the following disorders:

• rheumatic lesions of a degenerative or inflammatory nature ( rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and spondyloarthritis);
• pain affecting the spine;
• rheumatic disorders in the soft tissue area outside the joints;
• active phase of a gout attack;
• pain resulting from surgery or injury (accompanied by swelling and inflammation);
• severe forms of migraine attacks;
• colic of biliary or renal origin.

Release form

The release of the therapeutic substance is realized in the form of injection liquid - inside ampoules with a volume of 3 ml/75 mg. There are 5 such ampoules in a box.

Pharmacodynamics

In vitro tests of diclofenac Na did not suppress proteoglycan biosynthesis occurring within cartilage tissues at levels similar to those observed during therapy.

In case of inflammation associated with surgery or injury, the medication quickly eliminates pain (spontaneous or occurring during movement) and reduces swelling caused by inflammation or a postoperative wound. [ 2 ]

The medicine has a significant analgesic effect in severe and moderate pain of non-rheumatic origin. Bioran can eliminate pain and reduce the intensity of blood loss in case of primary dysmenorrhea.

At the same time, the drug demonstrates high effectiveness in the development of migraine attacks.

Pharmacokinetics

Absorption.

When 75 mg of diclofenac is injected intramuscularly, it begins to be absorbed immediately. Cmax values in plasma, with an average level of about 2.5 μg/ml, are recorded after approximately 20 minutes. Immediately after this, the plasma value of the drug decreases rapidly. The volumes of the absorbed active ingredient have a linear dependence on the size of the portion of the drug.

When the drug is used repeatedly, its pharmacokinetics remain unchanged. If the prescribed intervals between administrations of the substance are observed, its accumulation does not occur.

Distribution processes.

Protein synthesis of the substance is 99.7% and is mainly realized with albumin (99.4%). The distribution volume is 0.12-0.17 l/kg.

Diclofenac is also detected inside the synovium (its Cmax values are observed here 2-4 hours later than inside the blood plasma). The imaginary half-life term from the synovium is 3-6 hours. After 2 hours from the moment of determining the plasma Cmax, the diclofenac level inside the synovium exceeds the intraplasmic marks, and these indicators remain higher for another 12 hours.

Exchange processes.

Metabolism of diclofenac is partially realized through glucuronidation of the unchanged molecule, but mainly through single and multiple methoxylation, causing the formation of several phenolic metabolic units (3'-hydroxy-, 4'-, 5'-, and also 4' and 5 dihydroxy- elements with 3'-hydroxy-4'-methoxydiclofenac), most of which are transformed into glucuronide conjugates. Two of these phenolic decay units have bioactivity, but their expression is much weaker than that of diclofenac.

Excretion.

Systemic drug clearance rates are 263±56 ml per minute. The terminal half-life is 1-2 hours. The half-life of 4 metabolic elements (including 2 components with therapeutic activity) is also short-lived and is 1-3 hours. At the same time, 3'-hydroxy-4'-methoxydiclofenac has a longer half-life, but it has no therapeutic effect at all.

About 60% of a dose of Bioran is excreted in the urine in the form of conjugates (glucuronic type) of the unchanged active ingredient, and along with this in the form of metabolic components, most of which are also glucuronic conjugates.

Less than 1% of excreted diclofenac is in unchanged form. The remainder of the drug is excreted in the form of decay components with feces and bile.

Dosing and administration

The medication is prescribed for intramuscular injections - deep into the gluteal muscle. It is prohibited to administer injections for more than 2 days in a row. If necessary, therapy is continued using Bioran tablets.

During the injection, in order to avoid damage to other tissues or nerves in the area of the procedure, it is necessary to follow these rules. The medication is injected deep into the outer upper quadrant of the gluteal muscle. The dose size is usually 75 mg (the volume of 1 ampoule), with 1-time use per day.

In severe cases (for example, in the case of colic), as an exception, 2 injections at a dosage of 75 mg can be administered, with an interval of several hours (the 2nd injection should be administered in the other buttock).

Alternatively, you can use the following regimen: an injection of the drug (75 mg per day) alternates with oral administration of Bioran tablets (the maximum daily dose is 0.15 g).

• Application for children

It is prohibited to use the medicine in pediatrics (under 18 years of age).

Use Bioran during pregnancy

Bioran is not prescribed during pregnancy.

If it is necessary to use the drug during breastfeeding, a decision must first be made to stop breastfeeding.

Contraindications

Main contraindications:

• an ulcer affecting the gastrointestinal tract;
• severe intolerance to diclofenac or other components of the drug (including sodium metabisulfate);
• people with an allergic reaction to the use of aspirin or other NSAIDs (allergy symptoms include urticaria, asthma attacks, or an active runny nose).

Side effects Bioran

Side effects include:

• disorders affecting the gastrointestinal tract: nausea, dyspepsia, flatulence, epigastric pain and anorexia sometimes occur, as well as abdominal cramps, diarrhea and vomiting. Ulcers in the gastrointestinal tract (may or may not be accompanied by perforation/bleeding) and gastrointestinal bleeding (melena, vomiting or bloody diarrhea) are occasionally observed. Glossitis, stomatitis, disorders associated with the lower intestine (including pancreatitis, obstipation, non-specific hemorrhagic colitis and the active phase of transmural ileitis or ulcerative colitis), and changes in the functioning of the esophagus, as well as the appearance of diaphragm-like strictures inside the intestine, may develop;
• CNS-related lesions: dizziness (sometimes severe) or headaches sometimes occur. Drowsiness is occasionally observed. Memory impairment, insomnia, tremor, disorientation, sensory disturbances (for example, paresthesia), depression and nightmares may develop, as well as seizures, anxiety, irritability, psychotic symptoms and aseptic meningitis;
• disorders of the sensory organs: possible hearing disorders, tinnitus, visual disturbances (diplopia or blurred vision) and taste disorders;
• signs of allergy: sometimes epidermal rashes are observed. Occasionally, urticaria develops. Eczema or blistering rashes may appear;
• renal dysfunction: edema occasionally occurs. Acute renal failure, tubulointerstitial nephritis, changes in urinary sediment (proteinuria or hematuria), nephrotic syndrome or necrotic papillitis may occur;
• liver dysfunctions: serum aminotransferase values sometimes increase. Rarely, hepatitis develops (with or without jaundice). Fulminant hepatitis may occur;
• hematopoietic disorders: anemia (aplastic or hemolytic), leukopenia or thrombocytopenia and agranulocytosis may develop;
• intolerance symptoms: occasionally asthma or general anaphylactoid or anaphylactic manifestations appear (including a decrease in blood pressure). Pneumonia or vasculitis may develop;
• damage to the function of the cardiovascular system: chest pain, tachycardia and CHF may appear, or blood pressure may increase;
• Other: sometimes symptoms occur in the injection area (hardening or pain). Local necrosis or abscesses may occur in the injection area.

Overdose

There is no information that describes typical clinical symptoms that develop in case of poisoning with Bioran.

In acute intoxication with NSAIDs, symptomatic and supportive actions should be taken. For example, they are taken in case of renal failure, respiratory depression, decreased blood pressure, and gastrointestinal dysfunction. The likelihood that hemoperfusion, forced diuresis, or hemodialysis will help excrete NSAIDs is very low, because the active ingredients of these agents are largely synthesized with protein and participate in intensive metabolic processes.

Interactions with other drugs

Digoxin and lithium substances.

The drug may increase plasma levels of digoxin or lithium.

Diuretics.

Like other NSAIDs, Bioran can reduce the intensity of the diuretic effect. Administration together with potassium-sparing diuretic drugs can increase serum K values (with such a combination of drugs, this indicator should be constantly monitored).

NSAID medications.

Systemic use with NSAIDs may increase the incidence of adverse effects.

Anticoagulants.

Although the effect of the drug on anticoagulants has not been registered in clinical trials, there is some information noting an increased likelihood of bleeding in people who have used such combinations. Because of this, with such a combination, it is necessary to constantly and very carefully monitor the patient.

Hypoglycemic agents.

Clinical tests have shown that Bioran can be combined with hypoglycemic drugs without changing the therapeutic effect of the latter. However, there are some data on the occurrence of hyper- or hypoglycemia with such a combination, which required changing the dosage of antidiabetic drugs when administered with the drug.

Methotrexate.

NSAIDs should be used with caution if administered less than 24 hours before or after methotrexate administration, as this may increase its blood levels and potentiate its toxic activity.

Cyclosporine.

NSAIDs affect the processes of PG binding in the kidneys, which can potentiate the nephrotoxic properties of cyclosporine.

Antibacterial agents (quinolone derivatives).

There is some information about the occurrence of seizures in people who combined NSAIDs with quinolone derivatives.

Often, the liquid from Bioran ampoules is prohibited from being mixed with injection solutions of other medications.

Storage conditions

Bioran must be stored in a place closed to children, away from sunlight and moisture. Ampoules must not be frozen. Temperature values are maximum 25°C.

Shelf life

Bioran can be used within a 3-year period from the date of manufacture of the medicinal substance.

Analogues

Analogues of the drug are the following medications: Diclomelan, Difen, Artrex and Diclofenac with Diclorium, and also Veral, Diclonac and Dorosan with Voltaren, Diclofenacol and Diclac with Diclogen, as well as Diclo-F and Diclofenaclong. In addition, the list includes Diclobene, Dicloran with Diclovit, Ortofen and Diclomax with Sodium diclofenac, Penseid and Diclofen, as well as Remetan and Naklofen with Sanfinac, Naklof and Flector, Ortofer, Uniclofen and Ortoflex with Flotac, Revmavek, Feloran and Tabuk-Di.