Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravesical injection in the form of powder or porous mass of white, almost white or light yellow color; solvent - clear, colorless liquid; the finished product is a clear or slightly opalescent solution, from colorless to light yellow.
hexaminolevulinate hydrochloride 100 mg,
which corresponds to the content of hexaminolevulinate 85 mg
Solvent: sodium hydrogen phosphate 30.5 mg, potassium dihydrogen phosphate 29.2 mg, sodium chloride 351 mg, hydrochloric acid 1M 159.5 mg qs to pH 6.0 0.1, sodium hydroxide 1M qs to pH 6.0 0.1, water d / u - up to 50 ml.
1 ml of the finished p-ra contains 1.7 mg of hexaminolevulinate, which corresponds to a solution of hexamethanolivulinate at a concentration of 8 mmol / l.
100 mg - glass bottles (1) (complete with solvent (50 ml) - polypropylene bottles (1)) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
In vitro studies showed a significant increase in fluorescence intensity of porphyrins accumulated in urothelial cancer tissue after exposure to hexaminolevulinate. In humans, the use of the Hexwix В® preparation showed a higher degree of accumulation of porphyrins in the affected tissues of bladder urothelium than in healthy ones.
Cystoscopy in blue light makes it possible to detect a much larger number of tumor foci, incl. carcinoma in situ and foci of papillary cancer in the bladder compared to standard cystoscopy in white light. The incidence of carcinoma in situ using standard white light cystoscopy was 49.5%, and for cystoscopy in blue light, this was 95.0%. The efficacy of determining papillary tumors ranged from 85.4-94.3% for white light cystoscopy and 90.6-100% for cystoscopy in blue light.
After intravesical injection of hexaminolevulinate, an increase in the content of porphyrins in the cells of the affected tissues of the bladder wall is observed.Intracellular porphyrins (including protoporphyrin PpIX) are photosensitive, fluorescent compounds that emit red light under the influence of blue light. As a result, precancerous and cancerous lesions of the urothelium will glow red light against a blue background. In the inflamed areas, false fluorescence can be observed.
In vivo studies in rats after intravesical administration showed high concentrations of hexaminolevulinate in the wall of the bladder.
After intravesical administration of healthy volunteers with hexaminolevulinate, having a radioactive label of 14 C, the system bioavailability was about 5-10%; there was a two-phase elimination, with a primary T 1/2 of 39 min and a final T 1/2 of 76 h. A blood test showed no binding of Hexwix В® to erythrocytes. In vitro studies have shown that Hexwix В® has undergone rapid metabolism.
Gexvix В® is intended for diagnostic purposes only:
- for detection of cancer of the bladder, incl. carcinoma in situ, in patients with established bladder cancer or in the presence of a high degree of suspicion of the possibility of its occurrence on the basis of the results of screening cystoscopy or positive cytological analysis of urine.
Fluorescent cystoscopy in blue light should be used in addition to standard cystoscopy in white light, as a guide for taking biopsies.
The preparation should be prepared and applied only by qualified personnel. Before the administration of the drug should be emptied of the bladder.
Adults (including elderly patients)
The ready-to-use solution is for intravesical administration.
50 ml of a ready solution with a concentration of 8 mmol / l is inserted into the bladder through a catheter. The patient should hold fluid in the bladder for about 60 minutes. No later than 60 minutes after emptying the bladder, a cystoscopic examination in blue light should be started.
The study of patients should be conducted in both white and blue light to obtain a map of all affected areas of the bladder. Biopsies from the identified affected areas are usually taken in white light.
Only cystoscopy equipment can be used, which is equipped with the necessary filters that allow analysis by standard cystoscopy in white light and fluorescence cystoscopy in blue light (wavelengths 380-450 nm).
Doses of light radiation, which the patient receives during cystoscopy, can be different. As a rule, the doses of light radiation (white and blue light) vary in the range of 180-360 J at an intensity of 0.25 mW / cm 2 .
Preparation of the solution
Hexaminolevulinate in case of contact with skin may cause sensitization.
All operations should be performed using sterile equipment and in aseptic conditions.
1. Collect 50.0 ml of the solvent in a 50 ml sterile syringe.
2. Add about 10 ml of solvent to the vial with lyophilizate.
3. Without removing the needle from the vial and holding the vial tightly with the syringe, gently shake until completely dissolved.
4. Collect the entire prepared solution from the vial with lyophilizate into the syringe. Gently mix the contents.
5. The resulting solution is ready for use. The solution should be clear or slightly opalescent, colorless or pale yellow.
Only for single use.
The whole unused preparation is subject to destruction.
Most side effects were mild to moderate in severity and transient in nature. The most common side effect is bladder spasm seen in 2.4% of patients, bladder pain (1.7% of patients), dysuria (1.8% of patients) and hematuria (1.7% of patients). The observed side effects were expected and are based on the experience of using standard cystoscopy and transurethral resection of the bladder.
Type of unwanted reaction Frequency * Undesirable reactions
Infections and infestations infrequently cystitis, sepsis, urinary tract infection
Mental disorders rarely insomnia
From the side of the nervous system is often a headache
Hepatobiliary disorders rarely increase the serum bilirubin content; increased activity of "hepatic" traysaminases
From the gastrointestinal tract often nausea, vomiting, constipation, diarrhea
From the side of skeletal musculature and connective tissue, infrequent back pain
Impaired kidney and bladder often bladder spasm, bladder pain, dysuria, urinary retention, hematuria.
infrequently pain in the urethra, pollakiuria, incontinence
On the part of the genitals and the breast, infrequently balanitis
Common disorders and conditions in the injection zone are often hyperthermia
Injuries, poisoning and procedural complications often pain at the site of drug administration
infrequently postoperative fever
From the side of the circulatory and lymphatic systems, infrequent leukocytosis, anemia
Metabolic disorders and nutritional functions infrequent gout
From the skin, infrequently the rash
* Very often: the incidence of complications is more than 1/10; often: the incidence of complications - 1 / 100-1 / 10; infrequently: the incidence of complications is 1 / 1000-1 / 100; rarely: the incidence of complications is 1 / 10000-1 / 1000; Very rarely: the incidence of complications is no more than 1 / 10,000; It is not known: the frequency can not be calculated on the basis of available data.
In post-marketing use, an anaphylactic shock was reported. The frequency is unknown.
- hypersensitivity to the active substance or any auxiliary component;
- women of reproductive age;
- Children under 18 years.
Repeated use of Gexwix В® during monitoring visits to patients with bladder cancer should be carried out with caution, since such studies have not been conducted.
Hexaminolevulinate should not be used if there is a high risk of inflammation of the bladder, for example, after BCG therapy (BCG - Calmette-Guerin bacillus), and with medium or severe leukocyturia.
PREGNANCY AND LACTATION
For hexaminolevulinate there are no clinical data on the use in pregnancy. Studies of reproductive toxicity in animals have not been conducted.
Hexaminolevulinate is not used in pregnant women. It is recommended to stop breastfeeding if you need to use the drug during this period.
APPLICATION FOR CHILDREN
The use of the drug for children and adolescents under the age of 18 is contraindicated.
In connection with the possibility of developing adverse reactions, incl. anaphylactic / anaphylactoid reactions at the time of drug administration, all conditions for immediate intensive care should be created in the room and if the hypersensitivity reaction develops, stop the drug immediately and, if necessary, start specific therapy.
From the microbiological point of view, the drug should be used immediately after preparation.
If the product has not been used immediately, medical personnel are responsible for the time and storage conditions before use. These indicators usually should not exceed 2 hours at a temperature of 2-8 В° C.
Before the introduction of the drug should be expressed severe inflammation of the bladder with a standard cystoscopy. Inflammation can lead to increased accumulation of porphyrins, an increased risk of local toxicity in light and false fluorescence.
If the study in white light shows a pronounced inflammation of the bladder, the study in blue light is not carried out.
In patients who have recently undergone surgical procedures on the bladder, there is an increased risk of false fluorescence in the area of вЂ‹вЂ‹resection.
Influence on ability to drive vehicles and work with machines and mechanisms
The effect of using the drug in applying it in accordance with the instruction for medical use on the ability to drive vehicles, as well as machines and mechanisms, has not been established.
No cases of overdose have been reported.
There were no reports of complications with prolonged exposure for more than 180 min (3 times the recommended infusion time), and in one case 343 min. There were no reported complications in the study of the effectiveness of different doses, when the concentrations of hexaminolevulinate were twice as high as those recommended.
There are no cases of using a higher intensity of light radiation or a longer exposure time.
Special studies of the interaction of hexaminolevulinate with other drugs have not been conducted.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of 2 В° C to 25 В° C. Store the prepared solution at a temperature of 2 В° C to 8 В° C. Shelf life - 3 years.The final solution should be used within 2 hours.
Do not use after the expiration date printed on the package.