Boramilan FS

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Instructions for use:

1. Release form and composition
2. Indications for use
3. Contraindications
4. Method of application and dosage
5. Side effects
6. Special instructions
7. Drug interactions
8. Terms and conditions of storage

Lyophilisate for preparation of solution for intravenous and subcutaneous administration of Boramilan FS

Boramilan FS is an antineoplastic drug.

Release form and composition

Dosage form - lyophilisate for the preparation of a solution for intravenous (i / v) and subcutaneous (s / c) administration: almost white or white powder with a porous structure [2.5 mg, 3 mg or 3.5 mg each in dark glass vials volume of 10 ml, in a blister strip packaging 1 bottle complete with 1 ampoule (5 ml) of solvent (or without it), in a cardboard box 1 package].

1 bottle contains:

active substance: bortezomib (three-dimensional form of boroxin) - 2.5 mg, 3 mg or 3.5 mg, calculated as bortezomib in the form of a monomer;
auxiliary component: D-mannitol.

Solvent: 0.9% sodium chloride solution.

Indications for use

mantle cell lymphoma (after the first line of therapy);
multiple myeloma.

Contraindications

During pregnancy and breastfeeding;
age up to 18 years;
damage to the pericardium;
acute form of diffuse infiltrative lung diseases;
individual intolerance to bortezomib, mannitol and boron.

Boramilan FS should be used with caution in case of severe renal dysfunction, severe and moderate liver dysfunction, fainting, seizures or epilepsy in history, diabetic neuropathy in history, constipation, dehydration against the background of vomiting or diarrhea, risk of chronic heart failure, with concomitant therapy with antihypertensive, oral hypoglycemic drugs, inhibitors or substrates of the CYP3A4 isoenzyme, substrates of the CYP2C9 isoenzyme.

Method of administration and dosage

Use Boramilan FS in strict accordance with the rules for handling anticancer drugs!

The ready-made lyophilisate solution is intended for intravenous and subcutaneous administration.

The concentration of 1 ml of solution for intravenous administration should be 1 mg, for s / c - 2.5 mg.

The lyophilisate can only be dissolved in 0.9% sodium chloride solution!

A solution for intravenous administration is prepared by mixing the contents of the vial with the corresponding volume of 0.9% sodium chloride solution (2.5 ml, or 3 ml, or 3.5 ml).

For subcutaneous administration, the contents of the vial at a dose of 2.5 mg are dissolved in 1 ml of 0.9% sodium chloride solution, at a dose of 3 mg - in 1.2 ml, at a dose of 3.5 - in 1.4 ml.

After dissolving the drug, the resulting solution should be clear and colorless. In the presence of color or any inclusions, the solution cannot be used.

The intravenous solution is injected through a central or peripheral venous catheter bolus for 3-5 seconds, the catheter is then flushed with 0.9% sodium chloride solution.

S / c the drug is injected into the left or right area of the thigh or abdomen, constantly changing the place for the next injection and retreating from the previous point at least 2.5 cm.

It is impossible to inject the drug s / c into sensitive, damaged (redness, bruising) areas of the body. In the event of local reactions, it is possible to reduce the concentration of the solution or transfer the patient to intravenous administration of Boramilan FS.

Recommended dosage for monotherapy: the initial dose is 1.3 mg per 1 m ² of body surface area on days 1, 4, 8 and 11, followed by a 10-day break. 1 cycle is 21 days. The procedure for administering the drug should always be carried out at the same time of day, the interval between injections should not be less than 72 hours. The clinical response is assessed after the third and fifth cycles of therapy.

Patients with a complete clinical response are additionally prescribed 2 cycles of treatment.

If the treatment lasts more than 8 cycles, in addition to the standard regimen, a maintenance therapy regimen can be used with the introduction of the drug on days 1, 8, 15 and 22 followed by a rest period of 13 days (from 23 to 35 days).

If the disease progresses after 2 cycles or stabilization after 4 cycles of therapy, Boramilan FS can be prescribed in combination with high doses of dexamethasone to achieve a clinical response. Dexamethasone is taken orally: 20 mg on the day of bortezomib administration and 20 mg on the next day after administration. The total dose of dexamethasone for 3 weeks (1, 2, 4, 5, 8, 9, 11 and 12 days) is 160 mg.

If, while using the drug, the patient is diagnosed with any non-hematological toxic effect of the 3rd degree (except for neuropathy) or hematological toxicity of the 4th degree has developed, the treatment should be suspended. After the symptoms of toxicity have been removed, treatment should be resumed at a dose reduced by 25%. If intoxication persists or reappears at the minimum dose, then the doctor should decide on the advisability of further use of the drug.

If neuropathic pain and / or peripheral sensory neuropathy occurs while using bortezomib, the dose should be changed.

Recommended single dose adjustment for the development of peripheral motor or sensory neuropathy and / or neuropathic pain, taking into account their severity:

Grade 1 with paresthesia and / or extinction of reflexes without loss of function and pain: no correction required;
1 degree with pain or 2 degree with dysfunction, but maintaining daily activity: 1 mg per 1 m ² of body surface;
Grade 2 with pain or grade 3 with impaired daily activity: temporarily stop using the drug, after removing the symptoms of toxicity, resume therapy at a dose of 0.7 mg per 1 m ² with a frequency of administration once a week;
Grade 4 sensory neuropathy with risk of disability or life-threatening motor neuropathy or risk of paralysis: drug withdrawal.

No dose adjustment is required in renal failure. Boramilan FS must be administered after dialysis in order not to reduce the concentration of the drug in the blood.

With a mild degree of liver dysfunction, a change in the initial dose is not required.

In moderate and severe liver dysfunctions, the initial dose of the drug is adjusted taking into account the concentration of bilirubin in the blood. With an average degree of impairment [with a level of bilirubin exceeding 1.5-3 times the upper limit of normal (ULN)] and severe (with a level of bilirubin more than 3 times higher than ULN), the patient is prescribed the drug at a dose of 0 during the first cycle, 7 mg per 1 m ². In the following cycles, a single dose is prescribed taking into account the tolerability of the drug: either it is increased to 1 mg per 1 m ² of body surface, or reduced to 0.5 mg per 1 m ².

For patients with previously untreated multiple myeloma, Boramilan FS is used in combination with oral administration of prednisone and melphalan. 1 cycle of therapy consists of 6 weeks, a total of 9 cycles are carried out. The frequency of application of the drug from 1 to 4 cycles is 2 times a week, from 5 to 9 cycles - 1 time per week.

A blood test should be performed before starting each cycle of combination therapy. Treatment can be started if the platelet count is above 70,000 / μl, the absolute neutrophil count (ASN) is more than 1000 / μl. Non-hematological toxicity should be grade 1 or baseline.

If blood counts are less than normal or non-hematological toxicity is higher than grade 1, correction of the dosage regimen is required.

Side effects

from the blood and lymphatic system: very often - neutropenia, anemia, thrombocytopenia; often - lymphopenia, leukopenia; infrequently - pancytopenia, febrile neutropenia, thrombocytopenic purpura, lymphadenopathy, hemolytic anemia; rarely - syndrome of disseminated intravascular coagulation (DIC syndrome); frequency unknown - leukocytosis, coagulopathy;
from the side of the vessels: often - hematoma, phlebitis, decreased blood pressure (BP), increased blood pressure, postural (orthostatic) hypotension; infrequently - hot flushes, vasculitis, purpura, intracerebral hemorrhage, petechiae, subarachnoid hemorrhage, intracranial hemorrhage, vein discoloration, stroke, ecchymosis, vein swelling, wound bleeding; rarely - embolism of peripheral vessels, pulmonary embolism; frequency unknown - thrombophlebitis, deep vein thrombosis;
from the heart: often - myocardial infarction, cardiogenic shock, angina pectoris, cardiac arrest, ventricular hypokinesia, development and exacerbation of chronic heart failure, pulmonary edema (including acute form), complete atrioventricular block, sinus node arrest, palpitations, tachycardia (including sinus and supraventricular), atrial fibrillation, arrhythmia; infrequently - atrial flutter, bradycardia, pulmonary hypertension, stagnation of blood in the pulmonary circulation; rarely - pericarditis, decreased left ventricular ejection fraction, ventricular arrhythmias, cardiac tamponade;
from the gastrointestinal tract (GIT): very often - decreased appetite, nausea, vomiting, constipation, diarrhea; often - hiccups, dyspepsia, dry mouth, stomatitis, pain in the abdomen, loose stools, flatulence, sore throat and pharynx; infrequently - colitis, increased appetite, belching, esophagitis, acute pancreatitis, melena, enteritis, bleeding from the gastrointestinal tract, paralytic intestinal obstruction, dysphagia, petechiae of the oral mucosa, pain in the spleen, gastritis, gastroesophageal reflux, hypersecretion on saliva tongue, discoloration of the tongue, ulceration on the tongue; rarely - cheilitis, ischemic colitis, ascites, peritonitis;
from the nervous system: very often - headache, paresthesia, peripheral neuropathy; often - dizziness (not including vertigo), tremor, polyneuropathy, hypesthesia, taste perversion, dysesthesia; infrequently - convulsions, fainting, paresis, peripheral motor neuropathy, paraplegia, loss of taste, impaired concentration, cognitive impairment, drowsiness, postural dizziness, speech disorders, mononeuropathy, restless legs syndrome; rarely - autonomic neuropathy, encephalopathy, posterior reversible leukoencephalopathy syndrome;
from the respiratory system, chest and mediastinal organs: very often - shortness of breath; often - cough, shortness of breath during exertion, rhinorrhea, nosebleeds; infrequently - hypoxia, tachypnea, nasal congestion, respiratory arrest, bronchospasm, wheezing, pleural effusion, respiratory alkalosis, pain in the paranasal sinuses, rhinitis, hoarseness, orthopnea, hemoptysis, hyperventilation, feeling of tightness in the chest, pain; rarely - pneumonitis, pneumonia (including interstitial), pulmonary hypertension, acute respiratory failure syndrome, respiratory failure, acute diffuse infiltrative lung damage, alveolar hemorrhage in the lung;
from the kidneys and urinary tract: often - dysuria, impaired renal function; infrequently - oliguria, renal failure (including acute form), renal colic, proteinuria, hematuria, frequent urination, urinary retention, difficulty urinating, urinary incontinence, back pain;
from the liver and biliary tract: infrequently - hypoproteinemia, hyperbilirubinemia, hepatitis, hepatic hemorrhage, increased activity of aspartate aminotransferase and alanine aminotransferase; rarely - hepatomegaly, liver failure, cholelithiasis, cytomegalovirus hepatitis;
on the part of the psyche: often - depression, insomnia, confusion, anxiety; infrequently - delirium, hallucinations, agitation, mood swings, sleep disturbances, changes in mental status, unusual dreams, irritability; rarely - disorder of orientation, suicidal mood, decreased libido, delirium;
on the part of the organ of vision: often - pain in the eyes, decreased clarity of vision; infrequently - dry eyes, hemorrhage in the eye, conjunctivitis, visual disturbances, photophobia, eye irritation, conjunctival hyperemia, increased lacrimation; rarely - ophthalmic herpes, blindness, optic neuropathy; frequency unknown - diplopia;
on the part of the organ of hearing and labyrinthine disorders: often - vertigo; infrequently - hearing impairment, ringing in the ears; rarely - bilateral deafness;
from the endocrine system: infrequently - a violation of the secretion of antidiuretic hormone (ADH); rarely - hypothyroidism; frequency unknown - hyperthyroidism, hypercortisolism;
from the musculoskeletal and connective tissue: very often - myalgia; often - muscle cramps, muscle weakness, pain in the limbs, musculoskeletal pain, bone pain, back pain, arthralgia; infrequently - muscle stiffness, muscle spasms and / or twitching, joint stiffness, joint swelling, pain in the jaws;
metabolic disorders: often - hypokalemia, dehydration, hyperglycemia; infrequently - hypocalcemia, cachexia, hyperkalemia, hypercalcemia, hypernatremia, hypoglycemia, hypophosphatemia, hyponatremia, hyperuricemia, hypomagnesemia, vitamin B ₁₂ deficiency;
on the part of the immune system: infrequently - hypersensitivity; rarely - amyloidosis, anaphylactic shock, Quincke's edema;
from the reproductive system: infrequently - erectile dysfunction, testicular pain; rarely - prostatitis;
dermatological reactions: very often - skin rash; often - itching, urticaria, periorbital edema, redness, itchy rash, increased sweating, eczema, dry skin; infrequently - photosensitivity, erythematous rash, bruising, macular rash, generalized pruritus, papular rash, generalized rash, psoriasis, swelling of the face and / or eyelids, dermatitis, nail damage, alopecia, changes in skin pigmentation, changes in hair structure, atopic dermatitis, nocturnal, nodules on the skin, ichthyosis; rarely - Sweet's syndrome (acute febrile neutrophilic dermatosis); very rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome;
laboratory and instrumental parameters: often - an increase in the activity of lactate dehydrogenase in the blood; infrequently - an increase in the concentration of urea in the blood, an increase in the activity of alkaline phosphatase, an increase in the activity of gamma-glutamyltransferase, a decrease in the level of hydrocarbonates in the blood, an increase in the activity of blood amylase, an increase in the level of C-reactive protein; rarely - lengthening of the QT interval and other deviations from the norm of electrocardiography (ECG), violation of the indicator of the international normalized ratio, a decrease in gastric acidity, an increase in platelet aggregation, an increase in troponin I;
local reactions: infrequently - hyperemia and burning sensation at the injection site, pain, phlebitis; in case of extravasation, inflammation of the subcutaneous fat;
others: very often - an increase in body temperature, increased fatigue, fungal infections, herpes simplex, herpes zoster (including disseminated); often - weakness, feeling unwell, flu-like symptoms, asthenia, peripheral edema, weight loss, the addition of secondary infections, edema; infrequently - chills, groin pain, feeling of tightness and / or discomfort in the chest, neuralgia, increased body weight, complications associated with a catheter, tumor lysis syndrome; rarely - septic shock, herpetic meningoencephalitis; very rarely - progressive multifocal leukoencephalopathy.

It should be noted that the side effects of monotherapy and the use of bortezomib in combination with prednisone and melphalan are similar.

special instructions

Treatment should only take place under the supervision of a physician with experience in anticancer chemotherapy.

Do not inject the drug solution intrathecally!

A complete blood count with platelet counts and leukocyte counts should be performed both before the start of Boramilan FS and during each cycle of therapy.

If the platelet count during monotherapy is less than 25,000 / μl and in combination with melphalan and prednisolone is less than 30,000 / μl, therapy should be suspended. Hematologic toxicity can be treated with colony-stimulating factors, red blood cell and platelet transfusions.

Patients are advised to prescribe antiemetics and rehydration therapy to prevent nausea, vomiting, and dehydration. It is necessary to carefully maintain the water-electrolyte balance, in case of diarrhea - take antidiarrheal drugs.

Regular monitoring is required for the development or deterioration of neurological symptoms indicative of progressive multifocal leukoencephalopathy (PML), if the diagnosis is confirmed, the drug should be discontinued.

With neuropathy, the patient is prescribed supportive therapy. Symptoms of peripheral neuropathy include: discomfort and / or burning sensation, paresthesia, hyperesthesia, hypesthesia, weakness, neuropathic pain. With subcutaneous administration of bortezomib, the likelihood of neuropathy is lower than with intravenous administration.

If you feel lightheadedness, dizziness or fainting, the patient should consult a doctor, since these conditions may indicate the development of orthostatic hypotension, requiring a reduction in the dose of the drug and the appointment of concomitant therapy.

When the diagnosis of posterior reversible leukoencephalopathy syndrome is confirmed, the drug should be discontinued.

To reduce the frequency of reactivation of the Herpes zoster virus, prophylactic administration of antiviral agents is recommended.

Due to the risk of developing hyperuricemia, treatment should be accompanied by regular monitoring of the concentration of creatinine and uric acid in the blood plasma. For the purpose of prophylaxis, the patient is recommended to drink plenty of fluids, if necessary, prescribe allopurinol and drugs for alkalinizing urine.

When combined with hypoglycemic agents for oral administration, blood glucose levels should be carefully monitored and the dose of hypoglycemic agents should be adjusted in a timely manner.

During the treatment period, persons of childbearing age are advised to use reliable contraception.

With the development of reactions of the immunocomplex type (proliferative glomerulonephritis, serum sickness, polyarthritis with rash), the use of bortezomib should be discontinued.

Due to the risk of side effects (including dizziness, fainting, visual disturbances) during the period of treatment, the patient is advised to refrain from driving vehicles and mechanisms.

Drug interactions

The simultaneous use of Boramilan FS with other drugs is possible only as directed by the attending physician, this will avoid the development of undesirable effects.

Terms and conditions of storage

Store out of the reach of light at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

The ready-made solution is suitable for use within 8 hours at storage temperatures up to 25 ° C and natural light.

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!