Longidase lyophilisate d / prig. solution for injection 3000ME, No. 5

Adults as part of complex therapy for the treatment and prevention of diseases accompanied by connective tissue hyperplasia.

in gynecology: treatment and prevention of adhesions in the small pelvis with inflammatory diseases of the internal genital organs, incl. tubal peritoneal infertility, intrauterine synechiae, chronic endometritis;

in urology: treatment of chronic prostatitis, interstitial cystitis;

in surgery: treatment and prevention of adhesions after surgical interventions on the abdominal organs; hypertrophic scars after injuries, burns, operations, pyoderma; long-term non-healing wounds;

in dermatovenerology and cosmetology: treatment of limited scleroderma, keloid, hypertrophic, forming scars after pyoderma, trauma, burns, operations;

in pulmonology and phthisiology: treatment of pneumosclerosis, fibrosing alveolitis, tuberculosis (cavernous-fibrous, infiltrative, tuberculoma);

in orthopedics: treatment of joint contractures, arthrosis, ankylosing spondylitis, hematomas;

to increase bioavailability: with the joint administration of antibacterial drugs in urology, gynecology, surgery, dermatovenerology, pulmonology, to enhance the effect of local anesthetics.

S / c (near the lesion site or under scar tissue) or i / m at a dose of 3000 IU in a course of 5 to 25 injections (depending on the disease) with an interval between injections from 3 to 10 days.

The methods of application are chosen by the doctor depending on the diagnosis, the severity of the disease, the clinical course, the patient's age.

If necessary, it is recommended to repeat the course in 2-3 months.

In the case of treatment of diseases accompanied by a severe chronic productive process in the connective tissue, after the standard course, long-term maintenance therapy with LongidaseЃ 3000 IU is recommended with intervals between injections of 10-14 days.

To increase the bioavailability of medicinal and diagnostic agents, a dose of 1500 IU is recommended with preliminary (10Ц15 minutes) intramuscular or subcutaneous administration in the same place as the main drug.

Breeding

1. The contents of an ampoule or vial of LongidazaЃ 3000 IU are dissolved in 1Ц2 ml of a solution of procaine (0.25 or 0.5%). In case of intolerance to procaine, LongidazaЃ is dissolved in the same volume of 0.9% sodium chloride solution for injection or water for injection.

2. When used to increase bioavailability, the contents of an ampoule or vial of LongidazaЃ 3000 IU are dissolved in 2 ml, and with a dosage of 1500 IU - in 1 ml of 0.9% sodium chloride solution for injection.

Inject the solvent into a vial or ampoule slowly, hold for 2-3 minutes, mix gently without shaking so as not to foam the protein.

The prepared solution for parenteral administration cannot be stored. Do not administer intravenously!

Recommended regimens for prevention and treatment

For the prevention of adhesive disease and gross scarring after surgical interventions on the abdominal and pelvic organs - in / m at a dosage of 3000 IU 1 time in 3 days, a course of 5 injections. If necessary, the use of LongidazaЃ can be continued with a general course of up to 10 injections with the introduction of 1 time in 5 days.

For treatment

in gynecology:

- adhesions in the small pelvis with inflammatory diseases of the internal genital organs - 3000 IU intramuscularly 1 time in 3-5 days, course - 10-15 injections;

- tubal peritoneal infertility - 3000 IU i.m. in a general course of up to 15 injections: the first 5 injections - 1 time in 3 days, then - 1 time in 5 days;

in urology:

- chronic prostatitis - 3000 IU intramuscularly 1 time in 5 days, course - 10-15 injections;

- interstitial cystitis - 3000 IU intramuscularly 1 time per 5 days, course - up to 10 injections;

in surgery:

- adhesive disease after surgical interventions on the abdominal organs - in / m at a dosage of 3000 IU 1 time in 3-5 days, the course - from 10 to 15 injections;

- long-term non-healing wounds - in / m at a dosage of 3000 IU 1 time in 5 days, a course - 5-10 injections;

in dermatovenerology, cosmetology:

- limited scleroderma - 3000Ц4500 IU intramuscularly 1 time in 3-5 days, a course - up to 20 injections. The dosage and course are selected individually, depending on the clinical course, stage, localization of the disease and the individual characteristics of the patient;

- keloid, hypertrophic and forming scars after pyoderma, burns, operations, injuries - intra-cicatricial or subcutaneous (near the lesion site) administration at a dosage of 3000Ц4500 IU, once every 3 days, with a course of up to 15 injections. The dilution volume of LongidazaЃ is chosen by the doctor depending on the number of injection points. If necessary, the course can be continued according to the scheme 1 time in 5 days up to 25 injections. Depending on the area of ??the skin lesion, the age of scar formation, it is possible to alternate subcutaneous and intramuscular administration 1 time in 5 days at a dosage of 3000 IU, with a course of up to 20 injections;

in pulmonology and phthisiology:

- pneumosclerosis - 3000 IU i / m 1 time in 5 days, course - 10 injections;

- fibrosing alveolitis - intramuscularly at a dosage of 3000 IU once every 5 days, with a course of 15 injections, then - maintenance therapy - once every 10 days with a general course of up to 25 injections;

- tuberculosis - in / m at a dosage of 3000 IU 1 time in 5 days, course - up to 25 injections; depending on the clinical picture and the severity of the course of the disease, long-term therapy is possible (from 6 months to 1 year at a dosage of 3000 IU once every 10 days);

in orthopedics:

- joint contracture - s / c near the lesion site at a dosage of 3000 IU 1 time in 3 days, a course - from 5 to 15 injections;

- arthrosis, ankylosing spondylitis - s / c near the lesion at a dosage of 3000 IU 1 time per 3 days, a course of up to 15 injections, if necessary, treatment can be continued with injections 1 time per 5 days. The duration of maintenance therapy is chosen by the doctor depending on the severity of the disease;

- hematomas - s / c near the lesion site at a dosage of 3000 IU 1 time in 3 days with a course of up to 5 injections;

to increase bioavailability: with joint s / c or i / m administration with diagnostic or medicinal products (including antibiotics, chemotherapy drugs, anesthetics). LongidazaЃ is preliminarily administered for 10-15 minutes at a dosage of 1500 IU in the same way and in the same place as the main drug.

Lyophilisate for the preparation of a solution for injection in the form of a porous mass of white or white with a yellowish or brownish tinge, hygroscopic.

1 fl.

bovhyaluronidase azoxymer (longidaseЃ) 3000 IU

Excipients: mannitol - up to 20 mg.

• Acute infectious diseases without the combined use of antimicrobial agents;

• pulmonary hemorrhage and hemoptysis;

• fresh vitreous hemorrhage;

• malignant neoplasms;

• acute renal failure;

• age up to 18 years (there are no results of clinical studies);

• pregnancy;

• breastfeeding period;

• hypersensitivity to bovgialuronidase azoxymer and other components of the drug.

  When the drug is administered using physiotherapy procedures

• increased sensitivity to laser radiation and ultrasound exposure;

• photodermatitis;

• taking steroid hormonal drugs;

• inflammatory process in the area of ??the joints;

• somatic diseases in which physiotherapeutic procedures are contraindicated.

• The drug is prescribed with caution for chronic renal failure (used no more than 1 time per week).

pharmachologic effect

Bovhyaluronidase azoxymer is a conjugate of the proteolytic enzyme hyaluronidase with a high-molecular carrier from the group of poly-1,4-ethylenepiperazine N-oxide derivatives. Bovhyaluronidase azoxymer possesses the entire spectrum of pharmacological properties inherent in drugs with hyaluronidase activity. The specific substrate of hyaluronidase is glycosaminoglycans (hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate) - the 'cementing' substance of connective tissue. As a result of hydrolysis (depolymerization), the viscosity of glycosaminoglycans and the ability to bind water and metal ions decrease. As a result, the permeability of tissues increases, their trophism improves, edema decreases, hematomas resolve, the elasticity of scar-altered areas increases, contractures and adhesions are eliminated,increased joint mobility. The effect is most pronounced in the initial stages of the pathological process.

The clinical effect of bovhyaluronidase azoxymer is significantly higher than that of native hyaluronidase. Conjugation increases the resistance of the enzyme to the action of temperature and inhibitors, increases its activity and leads to prolongation of action. The enzymatic activity of bovhyaluronidase azoxymer is retained when heated to 37 ? C for 20 days, while native hyaluronidase under the same conditions loses its activity during the day. Bovhyaluronidase azoxymer also retains the pharmacological properties of the carrier, which has chelating, antioxidant, anti-inflammatory and immunomodulatory activity.

Bovhyaluronidase azoxymer is able to bind iron ions released during the hydrolysis of glycosaminoglycans - activators of free radical reactions, hyaluronidase inhibitors and collagen synthesis stimulators, and thereby suppress the reverse reaction aimed at the synthesis of connective tissue components. The polytropic properties of bovhyaluronidase azoxymer are realized in a pronounced anti-fibrotic effect, experimentally proven by biochemical, histological and electron microscopic studies on a pneumofibrosis model.

Bovhyaluronidase azoxymer regulates (increases or decreases, depending on the initial level) the synthesis of inflammatory mediators (interleukin-1 and TNF?), Is able to weaken the course of the acute phase of inflammation, increase the humoral immune response and the body's resistance to infection. These properties make it possible to use bovhyaluronidase azoxymer during or after surgical treatment in order to prevent gross scarring and adhesions. The use of bovgialuronidase azoxymer in therapeutic doses during or after surgical treatment does not cause a deterioration in the course of the postoperative period or the progression of the infectious process; does not slow down the restoration of bone tissue.

Bovgialuronidase azoxymer, when administered jointly by subcutaneous or intramuscular injection, increases the absorption of drugs, accelerates anesthesia with the introduction of local anesthetics.

Bovhyaluronidase azoxymer refers to practically non-toxic compounds, does not disrupt the normal functioning of the immune system, does not affect the reproductive function of male and female rats, on the pre- and postnatal development of offspring, does not have a mutagenic and carcinogenic effect. It has been experimentally proven that in bovhyaluronidase azoxymer the irritating and allergenic properties of the enzyme hyaluronidase are reduced. In therapeutic doses, bovhyaluronidase azoxymer is well tolerated by patients.

Pharmacokinetics

Absorption and distribution

When administered parenterally, bovhyaluronidase azoxymer is rapidly absorbed into the systemic circulation and reaches Cmax in the blood after 20-25 minutes. It is characterized by a high rate of distribution, the half-life is about 0.5 hours. Penetrates into all organs and tissues (including through the BBB and the blood-ophthalmic barrier).

Apparent Vd - 0.43 l / kg. Conjugation does not reduce the high bioavailability of the enzyme - the bioavailability is not less than 90%.

Metabolism and excretion

In the body, hyaluronidase undergoes hydrolysis, and the carrier is metabolized to low molecular weight compounds (oligomers), which are excreted mainly through the kidneys in two phases. During the first day, 45-50% is excreted through the kidneys, no more than 3% through the intestines. Further, the rate of excretion slows down, by 4-5 days the drug is completely excreted. T1 / 2 with intramuscular administration - 36 hours, with subcutaneous administration - about 45 hours.

Side effect

Skin and subcutaneous tissue disorders: infrequently - skin redness, itching and swelling at the injection / application site. All local reactions go away on their own after 48-72 hours.

General disorders and conditions at the injection site: often - soreness at the injection site.

From the immune system: very rarely - allergic reactions, incl. immediate type.

Laboratory and instrumental data: very rarely - an increase in body temperature is possible.

If there are any side effects that are not indicated in the instructions, the patient should be informed about this by the doctor.

Application during pregnancy and lactation

The use of LongidazaЃ is contraindicated in pregnant women and women during breastfeeding.

Application for impaired renal function

The use of the drug is contraindicated in acute renal failure.

In chronic renal failure, the drug is prescribed no more than 1 time per week.

Application in children

The drug is contraindicated under the age of 18.

special instructions

If an allergic reaction develops, the patient should stop using LongidazaЃ and consult a doctor.

If it is necessary to stop taking the LongidazaЃ drug, cancellation can be carried out immediately, without a gradual dose reduction.

If the next dose of the drug is missed, its subsequent use should be carried out as usual, as indicated in this instruction or recommended by a doctor. The patient should not enter a double dose in order to compensate for missed doses.

The drug should not be used if there are visual signs of its unsuitability (packaging defect, powder discoloration).

Do not inject LongidazaЃ into the area of ??acute infectious inflammation due to the risk of spreading a localized infection.

In the case of treatment of diseases accompanied by a severe chronic productive process in the connective tissue, after a standard course, long-term maintenance therapy with LongidazaЃ 3000 ME is recommended with intervals between injections of 10-14 days.

Influence on the ability to drive vehicles and mechanisms

The use of LongidazaЃ does not affect the ability to perform potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

Overdose

Overdose symptoms can be manifested by chills, fever, dizziness, and decreased blood pressure.

Treatment: the administration of the drug is stopped and symptomatic therapy is prescribed.

Drug interactions

Bovgialuronidase azoxymer can be combined with antibiotics, antiviral, antifungal drugs, bronchodilators.

When used in combination with other drugs (antibiotics, local anesthetics, diuretics), bovhyaluronidase azoxymer increases bioavailability and enhances their effect.

When used together with large doses of salicylates, cortisone, ACTH, estrogens or antihistamines, the enzymatic activity of bovhyaluronidase azoxymer may be reduced.

Do not use bovhyaluronidase azoxymer simultaneously with furosemide, benzodiazepines, phenytoin.