Ribomustin 100 Janssen treats chronic lymphocytes, lymphoma without Hodgkin, multiple tumors

Dosage form Box
Specifications Bendamustine hydrochloride

Ingredient

Composition information	Content
Bendamustine hydrochloride	100mg

Uses

Indications

Chronic lymphocytes: Treatment for step one for chronic lymphocytes (stage B or C according to binet) in patients inappropriate chemotherapy in combination with fludarabin.

Hodgkin non -lymphoma: Hodgkin tumor does not progress slowly in patients with progressive disease after treatment with rituximab or chemotherapy in combination with rituximab.

Multi-marrow tumor: Treatment for step one for multi-marrow tumor (Durie-Salmon classification of phase II has progressed or phase III) in collaboration with Prednison in patients over 65 years old without suitable for self-stem cell transplantation and patients with clinical neurological diseases at the time of diagnosis without being able to use Bortezomib or Thalidomid treatment.

Pharmacokinatus

Medicine group treatment: Anti -cancer drugs, Alkyl group, ATC code: L01AA09

Bendamustin is an anti -tumor alkyl group with a unique activity in that containing benzimidazole is like purin. Bendamustin's anti -cancer and cytotoxic effects are mainly based on the cross -connection of single and double DNA fibers with alkylation. As a result, the DNA double function, synthesized and repaired DNA is broken. Bendamustin is active against both types of cells: cells that are dividing and inactive cells.

Bendamustin's exact operation mechanism is still unknown. Bendamustin Hydrochlorid's anti-tumor effect is proved in some in-vitro studies on many different tumor cell lines in humans (breast cancer, small cell lung cancer and no small cells, ovarian carbin and other leukemia) and in-vivo on many different types of experimental tumors originating from rats, mice, cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer, soft cancer lymphoma, leukemia and small cell lung cancer).

Bendamustin Hydrochlorid shows the activity on tumor cells in other people with other alkyl groups. The active ingredient of the drug shows that there is no or very little diagonal resistance to tumor cell lines in humans with different resistance mechanisms at least partly due to the relatively sustainable interaction with DNA. Moreover, clinical studies show that there is no completely Bendamustin cross resistance with anthracyclin, alkyl or rituximab drugs. However, the number of patients is considered small.

pharmacokinetics

Distribution

After 30 minutes of intravenous infusion, the center of the center is 19.3 L. In a stable condition after rapid intravenous injection, the distribution volume is 15.8-20.5 l.

Over 95% of the active ingredients are associated with plasma proteins (mainly albumin).

Metabolism

Bendamustin's main elimination line is hydrolyzed into monohydroxy- and dihydroxy-bendamustin. The formation of N-Desmethyl-Bendamustin and Gamma-Hydroxy-Bendamustin through metabolism in the liver thanks to isenzyme cytochrom P450 (CYP) 1A2. Bendamustin's other main metabolic line is tied to Glutathion.

In-Vitro, Bendamustin does not inhibit CYP 1A2, CYP 2C9/10, CYP 2D6, CYP 2E1 and CYP 3A4.

Elimination

Average average clearance after intravenous infusion 30 minutes at a dose of 120 mg/m of the body surface area for 12 testers is 639.4 ml/min. About 20% of the dose used in urine 24 hours. The amount of excretion in urine in order is: monohydroxy-bendamustin> bendamustin> dihydroxy-bendamustin> oxidation metabolic> N-Desmethyl Bendamustin. In the bile, the main metabolic products are eliminated polarity.

Hepatic failure

In patients with 30-70% of the liver is destroyed by tumor and mild liver failure (serum bilirubin

kidney failure

In patients with creatinine clearance> 10 ml/min, including patients with dialysis, there is no significant difference compared to patients with normal liver and kidney function in terms of CMAX, IMAX, AUC, T1/2B, distribution and clearance.

Elderly patients

Patients to 84 years of age are also included in pharmacokinetic studies. High age does not affect Bendamustin pharmacokinetics.

Before taking Ribomustin 100 Janssen treats chronic lymphocytes, lymphoma without Hodgkin, multiple tumors

How to use

oral tablets. Take the tablet with a glass of water.

Dosage

Use intravenous infusion for 30-60 minutes.

Chronic lymphocytes: Bendamustin Hydrochlorid 100 mg/m2 of the body surface area, on day 1 and 2 of cycles, each cycle of 4 weeks, up to 6 cycles.

Hodgkin lymphocytes: Bendamustin Hydrochlorid 120 mg/m2 of the body surface area, on day 1 and 2 of cycles, each 3 -week cycle, for at least 6 to 8 cycles (maximum periods of periods).

multi-tumor: Bendamustin Hydrochlorid 120-150 mg/m The body surface area, on day 1 and 2, coordinate with Prednison 60 mg/m2 The body surface area of the intravenous or oral surface from day 1 to 4 of cycles, each cycle of 4 weeks in at least 3 cycles.

Should delay or stop treatment if the number of white blood cells decreased by 3,000/UL and/or the number of platelets decreased 4,000/l and the number of platelets increased by> 100,000/l.

The lowest number of white blood cells and platelets measured after 14-20 days, recovered after 3-5 weeks.

Recommendations should closely monitor blood formulas during the non -treatment break (see warning and caution).

In the case of non -hematitis, the reduction of bureaucracy must be based on the worst toxicity level according to the common toxic standard (CTC) of the previous cycle. It is recommended to reduce the dose by 50% in case of level 3 toxicity according to CTC. Recommendation to stop treatment in case of toxicity of level 4 according to CTC.

If the dose is needed for a patient, the dose has been reduced for the patient alone to be used on day 1 and 2 of the corresponding treatment cycle.

Liver failure

Based on pharmacokinetic data, do not need to adjust the dose in patients with mild liver impairment (serum bilirubin Recommended 30% reduction in dosage in patients with average liver failure (serum bilirubin 1.2 - 3 mg/dl).

There is no data in patients with severe liver failure (serum bilirubin> 3 mg/dl) (see contraindicated).

kidney failure

Based on pharmacokinetic data, do not need to adjust the dose in patients with creatinine clearance> 10 ml/min. Experience in patients with severe renal failure is limited.

Pediatric patientsBendamustin's safety and effectiveness in pediatric patients have not been established due to limited data.

Elderly patients

There is no evidence that the dose adjustment is needed in elderly patients (see pharmacokinetics).What do

do when overdose? The event on the heart level 2 by CTC corresponds to the ECG changes that manifest myocardial ischemia is considered to the dose limit.

In the next study with Bendamustin transmitted for 30 minutes on day 1 and 2 every 3 weeks, the maximum tolerance of the drug is 180 mg/m2. The limit toxicity of the dose is a platelet reduction of 4th.

Handling measures

There is no specific antagonist. Bone marrow transplantation can be performed and transmit blood products (platelets, red blood cells) or use blood growth factors as effective measures to control side effects on hematology.

bendamustin hydrochlorid and metabolites are separated at a small level.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Side Effects

The most common adverse reactions when using Bendamustin Hydrochlorid is a hematological adverse reaction (leukopenia, thrombocytopenia), skin toxicity (allergic reactions), systemic symptoms (fever), gastrointestinal symptoms (nausea, vomiting).

A few cases of Stevens-Johnson syndrome and poisoned epidermal necrosis have been reported in patients using Bendamustin in combination with Allopurinol or combined with Allopurinol and Rituximab. In addition, some cases of hepatitis B regeneration lead to liver failure are reported in patients treated with Bendamustin. Reducing blood cells, headaches, dizziness is reported in patients treated with Bendamustin.

CD4/CD8 ratio may decrease. Also reduce the number of lymphocytes. In patients with immunodeficiency, the risk of infection may be increased (eg herpes zoster).

There have been individually reports on necrosis after accidentally transmitting drugs out of blood vessels and diagnostic necrosis, tumor syndrome and anaphylactic shock.

There are reports on secondary tumors including marrow dysplasia syndrome, marrow hyperactive disorder, acute marrow leukemia and bronchial carbin. However, the relationship with Ribomustin treatment has not yet been determined.

Notify the doctor with unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

Contraindicated

too hypersensitivity to active ingredients or any excipients.

breastfeeding.

Severe liver failure (serum bilirubin> 3 mg/dl).

jaundice.

Severe bone marrow failure and change in the number of serious blood cells (leukocytes decreased

Over the surgery less than 30 days before starting treatment.

Infection, especially with leukopenia.

Vaccination of yellow fever.

Caution when using

myeloma

Patients treated with Bendamustin Hydrochlorid may have marrow failure (bone marrow failure).

When the bone marrow failure is available, it is recommended to monitor leukemia, platelets, hemoglobin and neutral leukocytes and re -evaluate before starting the next treatment cycle. Before starting the next treatment cycle, recommend the following parameters:

Number of white blood cells> 4,000/UL and the number of platelets> 100,000/UL.

The marrow failure due to treatment may need to adjust the dose and/or delay the dose. Ribomustin should not be used when severe marrow failure or changes in serious blood cells.

Infections

There have been reports on infections, including pneumonia and bacterial infections. In some rare cases, infections are associated with the need for hospitalization, infections and death. Patients with marrow failure after treatment with bendamustin hydrochlorid are susceptible to infection. Patients with posteropuloma with Ribomustin are recommended to contact the physician if there are symptoms or signs of infection, including fever or respiratory symptoms.

Skin reaction

Some reactions on the skin have been reported. These events include rashes, toxic reactions on the skin and a variety of water balls. Some events occur when using Bendamustin in combination with other anti -cancer receipt, so it is unclear the exact relationship. When the reaction appears on the skin, if continued treatment, these reactions may progress and worsen; Therefore, it is necessary to closely monitor patients with skin reactions. If the skin reaction is serious or progressive, it is advisable to suspend or stop treating Ribomustin. For serious skin reactions that are suspected to be related to Bendamustin Hydrochlorid, it is advisable to stop treatment. There have been reports on cases of Stevens-Johnson syndrome and poisoned epidermal necrosis (Ten) when using Bendamustin simultaneously with allopurinol and other drugs known to this syndrome.

Patients with heart disorders

Strictly monitoring potassium concentration in the blood during treatment with Bendamustin Hydrochlorid and the potassium should be added when K+

Nausea, vomiting

Can take anti -vomiting drugs to treat nausea and vomiting symptoms.

Tumor solving syndrome

There have been reports on tumor solving syndrome related to Ribomustin in patients participating in clinical trials. This syndrome tends to occur within 48 hours of the first ribomustin dose and otherwise intervention can lead to acute renal failure and death. Preventive measures include adequate fluid condition, closely monitoring blood biochemistry, especially potassium and uric acid levels. It is possible to consider using allopurinol for 1 to 2 weeks of treatment with ribomustin but not necessarily a standard treatment.

Anaphylaxis

Reactions during transmission to Bendamustin Hydrochlorid often occur in clinical trials. In general, the symptoms are usually mild, including fever, chills, itching and rash. In some dangers, anaphylactic reaction or anaphylactic shock.

Ask the patient about the symptoms of a response due to the first transmission of the treatment cycle. The use of measures to prevent severe reactions, including antihistamine, fever and corticosteroid resistance in the next cycles in patients with previous infusion reactions.

Patients with allergic reactions 3 or worse than the typical cases are not used again.

contraception

Bendamustin Hydrochlorid is a mutant and teratogen.

Women should not be pregnant during treatment. Male patients should not have children during treatment and until 6 months after treatment. These patients should be advised on sperm preservation before treatment with ribomustin because it is likely to be infertile.

Swing

Should stop immediately if transmitted to the circuit. Should remove the needle after sucking a little. After that, apply cold compresses to be damaged and promote hand scenes. No clear benefits with supportive treatments such as corticosteroids.

Other malignancy

There have been reports on secondary tumors, including marrow disorders, marrow hyperactive disorders, acute leukemia and bronchial carcinoma. Bendamustin has not been identified.

Hepatitis B activity

There has been a report on hepatitis B regeneration including death and may appear hepatitis due to the reconstruction of hepatitis B virus B. It is recommended to apply appropriate measures to identify patients with hepatitis B before treatment with ribomustin, so regular monitoring of liver function and signs (Markers) hepatitis B should use appropriate drugs and/or preventive measures to prevent hepatitis B.

The effect of the drug on driving and operating machinery

has not conducted research on the effects of the drug on the ability to drive and operate machinery. However, the loss of movement air conditioning, peripheral neuropathy and chicken sleep have been reported when treated with ribomustin (see unwanted effects). Patients should be instructed to avoid dangerous jobs such as driving and operating machinery if they have the above symptoms.

Use drugs for women during pregnancy and lactation

Pregnant women

Not enough data on the use of ribomustin in pregnant women. On preclinical studies, Bendamustin is an embryo/fetal toxicity, monster and gene toxicity. Pregnant women must use effective contraception before, during and a month after treatment with ribomustin.

During pregnancy, ribomustin should not be used unless the benefits are out of risk. The mother should be known about the risk for pregnancy. If treated with ribomustin is absolutely necessary during pregnancy or if pregnant during treatment, patients should be known about the risk for a child who is not born and should be carefully monitored. Should consider genetic advice.

breastfeeding women

It is unclear whether Bendamustin will go through breast milk, so contraindicated ribomustin while breastfeeding (see contraindicated).

Must stop breastfeeding during treatment with ribomustin.

Reproduction

Men are treated with Bendamustin should be advised to have no children during treatment and 6 months after the end of treatment.

should advise on sperm preservation before treatment because the infertility may not recover when treated with ribomustin.

Drug interaction

There is no In-vivo interaction research.

When combining ribomustin with medication -causing medications, it can be likely to affect the bone marrow caused by ribomustin and/or medications used simultaneously. Any treatment that reduces patients' physical condition or osteoporosis can increase ribomustin toxicity.

Combining ribomustin with cyclosporin or tacrolimus can lead to excessive immunity inhibitors with the risk of lymphocytic proliferation.

Helping cells can reduce the formation of antibodies after viral immunization to reduce toxicity and increase the risk of infection that can lead to death outcome. This risk increases in those who have been inhibited immunity by their background pathology.

Bendamustin metabolism related to enzymes with the same cytochrom P450 (CYP) 1A2 function (see pharmacokinetic properties).

Therefore, there is a possibility of interacting with CYP1A2 inhibitors (such as fluvoxamin, ciprofloxacin, acyclovir, cimetidine).

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

To be out of reach of children, read the user manual carefully before use.

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