Longidaza

General characteristics. Structure:

Active agent - Longidaza®, substance (a hyaluronidase conjugate with copolymer of N-oxide of a 1,4-etilenpiperazin and (N-carboxymethyl) - bromide 1,4-etilenpiperaziniya) 1500 ME or 3000 ME

Excipient - Mannitolum to 15 mg (for a dosage 1500 ME) or to 20 mg (for a dosage 3000 ME).

Pharmacological properties:

Лонгидаза® represents a conjugate of proteolytic enzyme hyaluronidase with the high-molecular carrier from group of derivatives of N-oxide poly-1,4 - этиленпиперазина. Лонгидаза® has all range of the pharmacological properties inherent in medicines with gialuronidazny activity. Specific substrate of hyaluronidase are glikozaminoglikana (hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate) - the "cementing" substance of connecting fabric. As a result of hydrolysis (depolymerization) viscosity of glikozaminoglikan, ability to connect water and ions of metals decreases. As a result, permeability of fabrics increases, their trophicity improves, hypostases decrease, hematomas resolve, elasticity of the cicatricial changed sites increases, contractures and commissures are eliminated, mobility of joints increases. The effect is most expressed in initial stages of pathological process.

The clinical effect of the drug Longidaza® is much higher, than effect of native hyaluronidase. Conjugation increases resistance of enzyme to action of temperature and inhibitors, increases its activity and leads to action prolongation. Enzymatic activity of the drug Longidaza® remains when heating 37 °C within 20 days while native hyaluronidase in the same conditions loses the activity within a day. In the drug Longidaza® also pharmacological properties of the carrier having chelating, antioxidant, antiinflammatory and immunomodulatory activity remain. Лонгидаза® it is capable to connect the iron ions which are released at hydrolysis of glikozaminoglikan – activators of free radical reactions, inhibitors of hyaluronidase and stimulators of synthesis of collagen and by that to suppress the back reaction directed to synthesis of components of connecting fabric. Polytropic properties of the drug Longidaza® are implemented in the expressed antifibrous action experimentally proved biochemical, histologic and electronic microscopic examinations on pneumofibrosis model.

The drug Longidaza® regulates (raises or reduces depending on initial level) synthesis of mediators of an inflammation (interleykin-1 and a tumor alpha necrosis factor), it is capable to weaken a current of an acute phase of an inflammation, to raise a humoral immune response and resistance of an organism to an infection. The specified properties allow to use the drug Longidaza® in time or after surgical treatment for the purpose of prevention of rough scarring and commissural process. Use of the drug Longidaza® in therapeutic doses in time or after operational treatment does not cause deterioration in a current of the postoperative period or progressing of infectious process; does not slow down recovery of a bone tissue.

Лонгидаза® at joint hypodermic or intramuscular introduction increases absorption of drugs, accelerates anesthesia at administration of local anesthetics. Лонгидаза® treats almost nontoxic connections, does not break normal functioning of immune system, does not exert impact on reproductive function of males and females of rats, on pre-and post-natal development of posterity, does not possess mutagen and cancerogenic action. It is experimentally proved that in the drug Longidaza® the irritating and allergenic properties of enzyme hyaluronidase are reduced. In therapeutic doses of Longidaza® it is well transferred by patients.

Pharmacokinetics. At parenteral administration active agent is quickly soaked up in a system blood stream and reaches the maximum concentration in blood in 20-25 minutes, is characterized by the high speed of distribution in an organism. The semi-distribution period – about 0,5 hours, an elimination half-life (Т½) at intramuscular introduction of 36 hours, at hypodermic about 45 hours. The seeming volume of distribution of 0,43 l/kg. Conjugation does not reduce high bioavailability of enzyme - bioavailability not less than 90%.

Active ingredient gets into all bodies and fabrics, including through hematoencephalic and ophthalmic barriers.
In an organism hyaluronidase is exposed to hydrolysis, and the carrier breaks up before low-molecular connections (oligomers) which are removed preferential through kidneys in two phases. Within the first days through kidneys 45-50%, through intestines no more than 3% are removed. Further the speed of removal is slowed down, by 4-5 days drug is removed completely.

Indications to use:

The adult as a part of complex therapy for treatment and prevention of the diseases which are followed by a hyperplasia of connecting fabric.

- in gynecology: treatment and prevention of commissural process in a small basin at inflammatory diseases of internal generative organs, including pipe and peritoneal infertility, intrauterine synechias, a chronic endometritis;

- in urology: treatment of chronic prostatitis, intersticial cystitis;

- in surgery: treatment and prevention of commissural process after operative measures on abdominal organs; hypertrophic hems after injuries, burns, operations, pyodermas; it is long not healing wounds;

- in a dermatovenereology and cosmetology: treatment of a limited scleroderma, the keloid, hypertrophic, forming cicatrixes after a pyoderma, injuries, burns, operations;

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

- in orthopedics: treatment of a contracture of joints, arthroses, ankylosing spondylarthritis, hematomas;

- for increase in bioavailability: at joint administration of antibacterial drugs in urology, gynecology, surgery, a dermatovenereology, pulmonology, for strengthening of effect of local anesthetics.

Route of administration and doses:

Лонгидаза® it is applied subcutaneously (near the space of defeat or for the cicatricial changed fabrics) or intramusculary in a dose by 3000 ME course from 5 to 25 injections (depending on a disease) with an interval between introductions from 3 to 10 days.
Routes of administration are chosen the doctor depending on the diagnosis, disease severity, a clinical current, age of the patient. If necessary the repeated course in 2-3 months is recommended.
In case of treatment of the diseases which are followed by heavy chronic productive process in connecting fabric after a standard course the long maintenance therapy by the drug Лонгидаза® 3000 ME with breaks between injections of-10 - 14 days is recommended.
For increase in bioavailability of medicinal and diagnostic means the dose 1500 ME is recommended at intramuscular or hypodermic introduction, preliminary for 10-15 minutes, to the same place, as the main drug.

Cultivation:
1. Contents of an ampoule or a bottle of the drug Лонгидаза® 3000 ME dissolve in 1,0-2,0 ml of solution of Procainum (0,25% or 0,5%). In case of intolerance of Procainum the drug Longidaza® dissolve in the same volume of solution of sodium chloride 0,9% for injections or water for injections.
2. At use for the purpose of increase in bioavailability contents of an ampoule or a bottle of the drug Лонгидаза® 3000 ME dissolve in 2,0 ml, and with a dosage 1500 ME in 1,0 ml of solution of sodium chloride of 0,9% for injections.
Solvent needs to be entered into a bottle or an ampoule slowly, to sustain 2-3 minutes, to mix carefully, without stirring up not to make foam squirrels.
The prepared solution for parenteral administration is not subject to storage.
Not to enter intravenously!

The recommended schemes of prevention and treatment
 
• For prevention of an adhesive desease and rough scarring after operative measures on abdominal organs and a small pelvis intramusculary in a dosage of 3000 ME 1 times in 3 days a course of 5 injections. If necessary use of the drug Longidaza® can be continued by the general course to 10 injections at introduction of 1 times in 5 days.
• For treatment.

in gynecology:
- commissural process in a small basin at inflammatory diseases of internal generative organs intramusculary on 3000 ME 1 times in 3-5 days a course of 10-15 injections;
- pipe and peritoneal infertility intramusculary on 3000 ME general course to 15 injections: the first 5 injections of 1 times in 3 days, further 1 time in 5 days;

in urology:
- chronic prostatitis intramusculary on 3000 ME 1 times in 5 days, a course of 10-15 injections;
- intersticial cystitis intramusculary on 3000 ME 1 times in 5 days, a course to 10 injections;

in surgery:
- an adhesive desease after operative measures on abdominal organs intramusculary in a dosage of 3000 ME 1 times in 3-5 days a course from 10 to 15 injections;
- it is long not healing wounds intramusculary in a dosage of 3000 ME 1 times in 5 days a course of 5-10 injections;

in a dermatovenereology, cosmetology:
- a limited scleroderma intramusculary on 3000-4500 ME 1 times in 3-5 days a course to 20 injections. The dosage and a course are selected individually depending on the clinical course, a stage, localization of a disease and specific features of the patient;
- the keloid, hypertrophic and forming cicatrixes after a pyoderma, burns, operations, injuries: introduction of 1 times, intra cicatricial or hypodermic near the place of defeat, in 3 days, a course to 15 injections in a dosage 3000-4500 ME. The volume of cultivation of the drug Longidaza® is chosen the doctor depending on quantity of points of introduction. If necessary the course can be continued according to the scheme of 1 times in 5 days to 25 injections. Depending on the area of damage of skin, prescription of formation of a hem alternation of hypodermic and intramuscular introduction of 1 times in 5 days in a dosage 3000 ME, a course to 20 injections is possible.

in pulmonology and phthisiology:
- a pneumosclerosis intramusculary on 3000 ME 1 times in 5 days a course of 10 injections;
- a fibroziruyushchy alveolitis intramusculary in a dosage of 3000 ME 1 times in 5 days a course of 15 injections, further a maintenance therapy of 1 times in 10 days the general course to 25 introductions;

- tuberculosis intramusculary in a dosage of 3000 ME 1 times in 5 days a course to 25 injections; depending on a clinical picture and weight of a course of a disease long therapy is possible (from 6 months to 1 year in a dosage of 3000 ME 1 times in 10 days);

in orthopedics:
- contractures of joints subcutaneously near the place of defeat in a dosage of 3000 ME 1 times in 3 days a course from 5 to 15 injections;
- arthroses, an ankylosing spondylarthritis subcutaneously near the place of defeat in a dosage of 3000 ME 1 times in 3 days a course to 15 injections, if necessary treatment can be continued by injections of 1 times in 5 days. Duration of a maintenance therapy is chosen the doctor depending on disease severity;

- hematomas subcutaneously near the place of defeat in a dosage of 3000 ME 1 times in 3 days a course to 5 injections;
for increase in bioavailability: at joint hypodermic or intramuscular introduction with diagnostic or medicines (antibiotics, himiopreparata, anesthetics, etc.). Лонгидаза® it is entered previously in 10-15 minutes in a dosage in 1500 ME of same way and into the same place, as the main drug.

Features of use:

In need of the termination of administration of drug of Longidaza® cancellation can be carried out at once, without gradual reduction of a dose.
In case of the admission of introduction of the next dose of drug it is necessary to enter it as soon as the patient remembers it, after that drug should be used as usual. The patient should not enter the doubled dose for the purpose of compensation of the passed doses.

INFLUENCE OF DRUG ON CONTROL OF VEHICLES AND MECHANISMS
Does not exert impact.

Side effects:

Often (> 1/100, <1/10) - morbidity in an injection site. Sometimes (> 1/1000, <1/100) reactions in the place of an injection in the form of erubescence, an itch and hypostasis are possible. All local reactions die away in 48-72 hours. Very seldom (<1/10 000) allergic reactions.

Interaction with other medicines:

The drug Longidaza® can be combined with antibiotics, antiviral, antifungal drugs, bronchial spasmolytics. At use in a combination with other medicines (antibiotics, local anesthetics, diuretics) Longidaza® increases bioavailability and strengthens their action. At combined use with high doses of salicylates, a cortisone, adrenocorticotropic hormone (AKTG), estrogen or antihistaminic drugs enzymatic activity of the drug Longidaza® can be reduced.

It is not necessary to use the drug Longidaza® along with the drugs containing furosemide, benzodiazepines, Phenytoinum.

Contraindications:

Hypersensitivity to drugs on the basis of hyaluronidase, acute infectious diseases, pulmonary bleeding and a pneumorrhagia, a fresh vitreous hemorrhage, malignant new growths, a renal failure, age up to 18 years (results of clinical trials are absent).

WITH CARE
It is not necessary to administer the drug Longidaza® in a zone of an acute infectious inflammation because of danger of spread of the localized infection.
At a chronic renal failure apply not more often than 1 time a week.
At development of allergic reaction it is necessary to interrupt drug Longidaza® use.
Before an initiation of treatment report to the doctor about all medicines accepted by you.

PREGNANCY AND BREASTFEEDING
It is not necessary to use the drug Longidaza® to pregnant women and women during breastfeeding.

Overdose:

Symptoms of overdose can be shown by a fever, temperature increase, dizziness, hypotension. Administration of drug is stopped and appoint symptomatic therapy.

Storage conditions:

In the dry place protected from light at a temperature not over 15 ºС. To protect from children.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for injections on 15 mg (for a dosage 1500 ME) or on 20 mg (for a dosage 3000 ME) in ampoules or bottles with a capacity of 3 ml of dark glass of 1 hydrolytic class. On 5 ampoules or bottles with drug in a blister strip packaging from a film polyvinyl chloride. One blister strip packaging together with the application instruction in a pack from a cardboard. Or on 5 ampoules or bottles together with the application instruction in a pack from a cardboard with an insert from a cardboard.