Bartizar, lyophilizate 3.5mg

• multiple myeloma;
• mantle cell lymphoma.

Active ingredient

Composition

How to take, the dosage

Bartizar® in a dose of 3.5 mg is indicated for intravenous and subcutaneous administration.

In intrathecal administration, death has been reported.

In intravenous administration, the solution concentration should be 1 mg/ml. When administered subcutaneously, the solution concentration should be 2.5 mg/ml.
The solution concentration must be calculated very carefully due to the difference in concentrations between the intravenous solution and the solution for subcutaneous administration.

Monotherapy

Bartizar® is given intravenously (IV) by jetting for 3-5 seconds or subcutaneously (p/cm).

The recommended dose of Bartizar® is 1.3 mg/m² body surface area twice weekly for 2 weeks (days 1, 4, 8, and 11), followed by a 10-day break (days 12-21). There should be at least 72 hours between administering consecutive doses of Bartizar®.

The degree of clinical response is recommended to be evaluated after 3 and 5 cycles of treatment. If complete clinical response is achieved, 2 additional cycles of treatment are recommended.

If the duration of treatment is longer than 8 cycles, Bartizar® can be used according to the standard regimen or according to a maintenance regimen – weekly for 4 weeks (days 1, 8, 15, 22) followed by a 13-day rest period (days 23-35).

Patients in whom therapy with Bartizar® has shown no clinical response (disease progression or stabilization after 2 or 4 cycles, respectively) may be prescribed a combination of high-dose dexamethasone with bortezomib. In this case, 40 mg of dexamethasone is administered orally with each dose of Bartizar®: 20 mg on the day of administration and 20 mg the day after bortezomib administration. Thus, dexamethasone is administered on days 1, 2, 4, 5, 8, 9, 11, and 12, for a total of 160 mg over 3 weeks.

Recommendations for Dose and Administration of Bartizar®

If any Grade 3 non-hematologic toxicity or Grade 4 hematologic toxicity other than neuropathy develops, treatment with Bartizar® should be stopped. Once symptoms of toxicity have disappeared, treatment with the drug can be resumed at a dose reduced by 25% (dose of 1.3 mg/m² is reduced to 1.0 mg/m²; dose of 1.0 mg/m² is reduced to 0.7 mg/m²). If symptoms of toxicity do not disappear or reappear at the lowest dose, discontinuation of Bartizar® should be considered unless the benefit clearly outweighs the risk.

If neuropathic pain and/or peripheral sensory neuropathy associated with the use of Bartizar® occur, the dose of the drug should be changed according to Table 1. In patients with a history of severe neuropathy Bartizar® may be used only after careful assessment of the risk/benefit ratio.

Table 1. Recommended dose changes for development of Bartizar®-induced neuropathic pain and/or peripheral sensory or motor neuropathy

Combination therapy

Multiple myeloma in previously untreated patients who are not candidates for stem cell transplantation.

The recommended dose in combination with melphalan and prednisone

Bartizar® is given intravenously by injection for 3-5 seconds or subcutaneously in combination with oral melphalan and prednisone. Nine 6-week cycles are performed, with Bartizar® administered 2 times per week in cycles 1-4 (days 1, 4, 8,11, 22, 25, 29, and 32) and once per week in cycles 5-9 (days 1, 8, 22, and 29), Table 2.

Table 2. Recommended dosing regimen for Bartizar® used in combination with melphalan and prednisone in patients with previously untreated multiple myeloma who are not indicated for stem cell transplantation

Bartizar® 2 times per week (cycles 1-4) Week 1 2 3 4 5 6 Bartizar® 1.3 mg/m² day
1 – – daybr> 4 day
8 day
11 period
rest day
22 day
25 day
29 day
32 rest period
/td> melphalan 9 mg/m² +
prednisone 60 mg/m² day
1 day
2 /td> day
3 day
4 rest period Bartizar® once a week (cycles 5-9) Week 1 2 3 4 5 6 day
3 day
4 rest period

Recommendations for Dose Adjustment in Combination Therapy

Before starting a new cycle of treatment:

– platelet count should be ≥70×109/l,
– absolute neutrophil count (ANC) ≥1.0×109/l,
– non-hematologic toxicity should decrease to grade 1 or baseline.

Table 3. Dose adjustment for subsequent treatment cycles

For more information about melphalan and prednisone, see the medical instructions for these drugs.

Multiple myeloma in previously untreated patients who are candidates for stem cell transplantation.

The recommended dose

The recommended starting dose of bortezomib when used in combination with other medications is 1.3 mg/m² body surface area twice weekly for 2 weeks (days 1, 4, 8 and 11) followed by a 10-18 day break, which is 1 treatment cycle. Three to six such cycles are required. At least 72 hours should pass between administering consecutive doses of Bartizar®.

Dose adjustment in patients who are indicated for stem cell transplantation should follow the recommendations in Table 1.

Dosing instructions for medications used in combination with Bartizar® are listed in the appropriate instructions for medical use.

Recurrent multiple myelomaRecommended dose when used in combination with pegylated liposomal doxorubicin

The dose and dose adjustment instructions for Bartizar® are described in the monotherapy subsection above.

Pegylated liposomal doxorubicin is used at a dose of 30 mg/m² on day 4 of a 3-week Bartizar® cycle as a 1-hour intravenous infusion immediately after administration of bortezomib.

More information about pegylated liposomal doxorubicin can be found in the instructions for medical use of this medication.

The recommended dose when used in combination with dexamethasone

The dose and dose adjustment instructions for Bartizar® are described in the Monotherapy section above.

Dexamethasone is taken orally at a dose of 20 mg daily on the day of Bartizar® administration and the day after.

For more information about dexamethasone, see the instructions for medical use for this medication.

Retreatment of multiple myeloma

In case of relapse in patients who have previously responded to therapy with Bartizar® (monotherapy or combination therapy), therapy should be started at the highest tolerated dose.

Dosing instructions are described in the monotherapy subsection.

Previously untreated mantle cell lymphoma

The recommended dose when used in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone

The dose and dose adjustment instructions for Bartizar® are described in the Monotherapy subsection above.

Six cycles of therapy with bortezomib are required. If the patient first responds to therapy during the 6th cycle, an additional 2 cycles of Bartizar® therapy are recommended.

On day 1 of each 3-week cycle of Bartizar® therapy, the following drugs should be administered as intravenous infusions: rituximab at a dose of 375 mg/m², cyclophosphamide at a dose of 750 mg/m² and doxorubicin at a dose of 50 mg/m². Prednisone is taken orally at a dose of 100 mg/m² on days 1, 2, 3, 4 and 5 of each Bartizar® treatment cycle.

Dose adjustment during therapy of previously untreated mantle cell lymphoma

Before starting a new treatment cycle (except for cycle 1):

– platelet count must be ≥100,000/μL and absolute neutrophil count (ANR) ≥1500/μL
– hemoglobin concentration must be ≥8 g/dL (≥4.96 mmol/L)
– non-hematologic toxicity must be reduced to grade 1 or baseline

In case of development of Grade 3 hematologic toxicity or any Grade 3 non-hematologic toxic effect other than neuropathy, treatment with Bartizar® should be suspended. See Table 4 for guidance on dose adjustment.

Table 4. Dose adjustment during therapy in patients with previously untreated mantle cell lymphoma

Interaction

Special Instructions

Treatment with Bartizar® should only be given under the supervision of a physician experienced in the use of antitumor chemotherapy.

Bartizar® is indicated for intravenous and subcutaneous administration only. Do not administer intrathecally.

A complete blood count and platelet count should be performed before and during each cycle of therapy.

Thrombocytopenia/neutropenia

The therapy with Bartizar® may lead to thrombocytopenia and neutropenia. The lowest platelet count is usually observed on day 11 of the cycle and is restored by the beginning of the next cycle. A cyclic periodicity of decreasing and increasing platelet counts has been observed in clinical studies in patients with multiple myeloma or mantle cell lymphoma. There is no evidence of increasing thrombocytopenia or neutropenia with either dosing regimen. When platelet count < 25×109/l or concomitant use with melphalan and prednisolone, when platelet count ≤30×109/l, therapy with Bartizar® should be suspended. When platelet counts are restored, treatment should be continued at reduced doses with careful weighing of the possible benefits and risks of treatment. Colony-stimulating factors, platelet and red blood cell transfusions can be used to treat hematological toxicity.

Gastrointestinal disorders

In order to prevent nausea and vomiting, anti-emetics are recommended. Anti-diarrheal medications are prescribed if diarrhea occurs. To prevent or treat dehydration, patients should use rehydration therapy and maintain water-electrolyte balance.

Because of the possible development of intestinal obstruction, patients with constipation should be monitored on a dynamic basis.

Progressive multifocal leukoencephalopathy

There have been very rare cases with an unspecified cause of progressive multifocal leukoencephalopathy (PML) with fatal outcome when using bortezomib. Patients diagnosed with PML were treated with immunosuppressants before or at the same time as bortezomib. Most cases of PML were diagnosed within 12 months of starting bortezomib treatment. Particular attention is required regarding suspected PML symptoms that the patient may not notice themselves (e.g., cognitive, neurological, or psychiatric). If PML is suspected, further treatment with bortezomib should be suspended until the diagnosis of PML is excluded.

Peripheral neuropathy

If neuropathy occurs, maintenance therapy is given. The incidence of peripheral neuropathy usually peaks at cycle 5 of bortezomib treatment. If new or increased symptoms of peripheral neuropathy are present, dose reduction and change of the drug administration regimen may be required.

Patients should be continuously monitored for the possibility of neuropathy symptoms (burning sensation, hyperesthesia, hypoesthesia, paraesthesia, discomfort, neuropathic pain or weakness). Patients receiving bortezomib therapy with other drugs that contribute to neuropathy (including concomitant use of thalidomide) should be monitored at all times.

Convulsions

In patients with no history of seizures or epilepsy, infrequent cases of seizures have been described. Special caution is required when treating patients who have any risk factors for seizures.

Orthostatic hypotension

Bortezomib therapy is often accompanied by orthostatic hypotension. In most cases it is mild to moderate in severity and may be observed throughout treatment. Rarely, short-term loss of consciousness has been observed. Caution should be exercised when using bortezomib in patients with a history of syncope, diabetic neuropathy, receiving hypotensive drugs, as well as in patients with dehydration due to diarrhea or vomiting. Patients should be instructed to consult a physician in case of dizziness, “light-headedness” or fainting. If orthostatic hypotension develops, hydration, administration of glucocorticosteroids and/or sympathomimetics is recommended; if necessary, the dose of hypotensive drugs should be reduced.

Heart failure

The development or worsening of existing chronic heart failure has been described with the use of bortezomib. Fluid retention may predispose to the development of signs and symptoms of heart failure. Patients with risk factors or a history of heart disease should be closely monitored.

Hepatic failure

Cases of acute hepatic failure have been described in patients who have concomitantly taken other drugs as concomitant therapy with bortezomib. Such signs of liver dysfunction as increased “liver” enzymes activity, hyperbilirubinemia or hepatitis usually disappeared when bortezomib was withdrawn. In patients with symptoms of hepatic dysfunction, the drug should be prescribed at lower initial doses and monitored for toxicity, since bortezomib is metabolized by “hepatic” enzymes and its concentration may increase with moderate to severe hepatic dysfunction (see section “Dosage and administration”).

Peripheral reversible leukoencephalopathy syndrome

. Posterior reversible leukoencephalopathy syndrome, a rare, reversible neurologic disorder that may be accompanied by seizures, elevated blood pressure, headache, lethargy, confusion, blindness, and other visual and neurologic disturbances, has been reported in patients taking bortezomib. Magnetic resonance imaging of the brain is performed to confirm the diagnosis. If posterior reversible leukoencephalopathy syndrome develops, bortezomib should be discontinued. The safety of resuming treatment with bortezomib after previously diagnosed posterior reversible leukoencephalopathy syndrome is unknown.

Reactivation of Herpes zoster virus

The treating physicians should consider antiviral prophylaxis in patients receiving therapy with Bartizar®. Patients treated with bortezomib, melphalan and prednisone had higher rates of reactivation of Herpes zoster virus compared to patients treated with melphalan and prednisone (14% and 4% respectively). Antiviral prophylaxis significantly reduced the rate of reactivation of Herpes zoster virus.

Pulmonary dysfunction

In rare cases, acute diffuse infiltrative lung disease of unknown etiology, such as pneumonitis, interstitial pneumonia, pulmonary infiltration and acute respiratory failure syndrome, have been observed when using bortezomib. Some of these conditions have been fatal. If symptoms of pulmonary dysfunction occur, or if pre-existing symptoms worsen, patients should be diagnosed and treated immediately.

Bortezomib therapy with concomitant high-dose cytarabine (2 g/m² per day) by continuous 24-hour infusion is not recommended (may be fatal).

Tumor lysis syndrome

Due to the possible development of hyperuricemia associated with tumor lysis syndrome, patients are advised to monitor serum uric acid and creatinine concentrations during therapy. In order to prevent hyperuricemia, abundant drinking is recommended, and if necessary, allopurinol and urine alkalinization.

When using Bartizar® in patients concomitantly taking oral hypoglycemic agents, blood glucose concentrations should be monitored carefully and the dose of hypoglycemic agents should be adjusted, if necessary.

Immunocomplex reactions

In cases of immunocomplex reactions (serum sickness, polyarthritis with rash and proliferative glomerulonephritis) have been described. In these cases, treatment with bortezomib should be discontinued.

The use of reliable contraceptive methods is recommended during treatment of either sexual partner.

The generally accepted rules for handling cytotoxic drugs should be followed when working with Bartizar®.

Bortezomib treatment may cause dizziness, fainting, visual disturbances and other adverse events that may adversely affect driving and operating machinery. In case of occurrence of the described adverse events, you should refrain from performing the specified activities.

Synopsis

Contraindications

Side effects

The safety performance of bortezomib when used in monotherapy is similar to that of bortezomib in combination with melphalan and prednisone.

Serious adverse reactions were infrequently observed during therapy with bortezomib and included heart failure, tumor lysis syndrome, pulmonary hypertension, reversible posterior encephalopathy syndrome, and acute diffuse infiltrative pulmonary disease. In addition, autonomic neuropathy was observed in rare cases. The most common adverse reactions reported during therapy with bortezomib were: nausea, diarrhea, constipation, vomiting, increased fatigue, fever, thrombocytopenia, anemia, neutropenia, peripheral neuropathy (including sensory), headache, paresthesia, decreased appetite, shortness of breath, rash, herpes zoster and myalgia.

The following are side effects that have been considered likely or possibly related to the use of bortezomib.
Side effects are grouped by frequency of occurrence: very frequently (>1/10), frequently (≥1/100 to < 1/10), infrequently (≥1/1000 to < 1/100), rarely (≥1/10000 to < 1/1000), very rarely (< 1/10000), frequency unknown.

Infections and invasions: often – herpes simplex, herpes zoster (including disseminated and ophthalmoherpes), pneumonia, fungal infections; infrequent – infection, bacterial, viral infections, sepsis (incl. septic shock), bronchopneumonia, herpesvirus infection, herpetic meningoencephalitis, bacteremia (including

Bronchial pneumonia, herpesvirus infection, herpetic meningoencephalitis, bacteremia (including staphylococcal), barley, influenza, subcutaneous fatty tissue inflammation, infections associated with the use of medical devices, skin infections, ear infections, staphylococcal infections, dental infections; rarely – meningitis (including bacterial), Epstein-Barr virus infection, genital herpes, tonsillitis, mastoiditis, chronic fatigue syndrome.

Benign, malignant and unspecified neoplasms (including cysts and polyps): rarely – malignant neoplasms, plasmacytic leukemia, renal carcinoma, neoplasms, fungal mycosis, benign neoplasms.

Blood and lymphatic system disorders: very common – thrombocytopenia, neutropenia, anemia; common – leukopenia, lymphopenia; infrequent – pancytopenia, febrile neutropenia, hemolytic anemia, lymphadenopathy, coagulopathy, leukocytosis; rarely – disseminated intravascular coagulation syndrome (DIC-syndrome), thrombocytosis, high blood viscosity syndrome, platelet disorders, thrombocytopenic purpura, blood disorders, hemorrhagic diathesis, lymphocytic infiltration.

Immune system disorders: infrequent – Quincke’s edema, hypersensitivity; rarely – anaphylactic shock, amyloidosis, reactions with formation of immune complexes (type III).

Endocrine system disorders: infrequent – Icenko-Cushing’s syndrome, hyperthyroidism, antidiuretic hormone secretion disorders; rarely – hypothyroidism.

Metabolic and nutritional disorders: very common – decreased appetite; common – dehydration, hypokalemia, hyponatremia, hyponatremia, changes in blood glucose concentration, hypocalcemia, changes in enzyme activity; infrequent – tumor lysis syndrome, no weight gain, hypomagnesemia, hypophosphatemia, hyperkalemia, hypercalcemia, hypernatremia, changes in uric acid concentration, diabetes, fluid retention; rarely – hypermagnesemia, acidosis, disrupted water-electrolyte balance, excessive fluid accumulation, hypochloremia, hypovolemia, hyperchloremia, hyperphosphatemia, metabolic disorders, vitamin B group deficiency, vitamin B12 deficiency, gout, increased appetite, alcohol intolerance.

Mental disorders: frequently – mood disorders and disturbances, anxiety, disorders and sleep disorders; infrequently – mental status changes, hallucinations, psychotic disorder, confusion, agitation; rarely – suicidal thoughts, adjustment disorder, delirium, decreased libido.

Nervous system disorders: very often – neuropathy, peripheral sensory neuropathy, dysesthesia, neuralgia; often – motor neuropathy, loss of consciousness (including fainting). fainting), dizziness, perversion of taste, drowsiness, headache; infrequent – tremor, peripheral sensorimotor neuropathy, dyskinesia, balance disorder, memory loss (excl. dementia), encephalopathy, posterior reversible encephalopathy syndrome, neurotoxicity, seizures, postherpetic neuralgia, speech disorder, restless legs syndrome, migraine, sciatica, concentration disorder, pathological reflexes, parosmia; rarely – intracerebral hemorrhage, intracranial hemorrhage (incl. ч. subarachnoid hemorrhage), cerebral edema, transient ischemic attack, coma, autonomic nervous system imbalance, autonomic neuropathy, cranial nerve palsy, paralysis, paresis, preconsciousness, brain stem damage syndrome, cerebral circulation disorder, radicular syndrome, psychomotor hyperactivity, spinal cord compression, cognitive disorders, movement disorders, nervous system disorders, sciatica, salivation, muscle hypotonia.

An organ of vision: frequently – ocular edema, visual disturbances, conjunctivitis; infrequently – ocular hemorrhage, eyelid infections, eye inflammation, diplopia, dry eyes, eye irritation, eye pain, increased lacrimation, ocular discharge; rarely – corneal lesions, exophthalmus, retinitis, scotoma, eye lesions (including eyelids), dacryrio.eyelids), dacryoadenitis, photophobia, photopsia, optical neuropathy, various degrees of visual impairment (up to blindness).

Hearing and balance: frequently – vertigo; infrequently – tinnitus, hearing loss (up to deafness), discomfort in the ear; rarely – bleeding, vestibular neuronitis, ear damage.

Heart: infrequent – cardiac tamponade, cardiopulmonary shock, cardiac fibrillation (including atrial fibrillation), heart failure (including left and right ventricular), arrhythmia, tachycardia, palpitations, angina pectoris, pericarditis (including exudative pericarditis), cardiomyopathy, ventricular dysfunction, bradycardia; rarely – atrial flutter, myocardial infarction, atrioventricular block, cardiovascular disorders (including cardiogenic shock), pirouette-type ventricular tachycardia, unstable angina, coronary artery disease, sinus node arrest.

Vascular system: frequently – decreased arterial pressure, orthostatic hypotension, increased arterial pressure; infrequently – stroke, deep vein thrombosis, bleeding, thrombophlebitis (including superficial), circulatory collapse (including hypovolemic shock), phlebitis, tides, hematoma (including perirenal), decreased peripheral circulation, vasculitis, hyperemia (including ocular); rarely – peripheral vascular embolism, lymphedema, pallor, erythromelalgia, vasodilation, color changes in veins, venous insufficiency.

Respiratory system, chest and mediastinum disorders: frequently – dyspnea, nasal bleeding, upper and lower respiratory tract infections, cough; infrequently – pulmonary embolism, pleural effusion, pulmonary edema (including acute), pulmonary alveolar hemorrhage, bronchospasm, chronic obstructive pulmonary disease, hypoxemia, airway obstruction, hypoxia, pleurisy, hiccups, rhinorrhea, dysphonia, wheezing; rare – respiratory failure, acute respiratory distress syndrome, apnea, pneumothorax, atelectasis, pulmonary hypertension, hemoptysis, hyperventilation, orthopnea, pneumonitis, respiratory alkalosis, tachypnea, pulmonary fibrosis, bronchial disorders, hypocapnia, interstitial lung disease, lung infiltration, tightness in the throat, dry throat, increased secretion in the upper respiratory tract, throat irritation, upper respiratory cough syndrome.

Gastrointestinal tract: very common – nausea, vomiting, diarrhea, constipation; common – gastrointestinal bleeding (including mucous membrane bleeding), dyspepsia, stomatitis, GI disturbances, pain in the throat and pharynx, pain in the abdomen (including gastrointestinal pain and spleen pain), oral disorders, flatulence; infrequent – pancreatitis (including chronic), vomiting blood, lip swelling, GI obstruction (including intestinal obstruction), abdominal discomfort, ulceration of oral mucosa, enteritis, gastritis, gingival bleeding, gastroesophageal reflux disease, colitis (incl. ч. pseudomembranous colitis), ischemic colitis, inflammation of the mucous membrane of the gastrointestinal tract, dysphagia, irritable bowel syndrome, GI disorders, plaque on the tongue, GI motility disorders, salivary gland disorders; rarely – acute pancreatitis, peritonitis, tongue swelling, ascites, esophagitis, cheilitis, fecal incontinence, anal sphincter atony, fecaloma, ulceration and perforation of the gastrointestinal tract, gum hypertrophy, megacolon, rectal discharge, occurrence of blisters in the throat, lip pain, periodontitis, anal fissure, change in the defecation rate, proctalgia, stool disorders.

Hepatobiliary system disorders: frequently – changes in activity of “liver” enzymes; infrequently – hepatotoxicity (including liver disorders), hepatitis, cholestasis; rarely – liver failure, hepatomegaly, Budd-Chiari syndrome, cytomegalovirus hepatitis, liver bleeding, gallstone disease.

Skin and subcutaneous tissue disorders: common – rash, itching, erythema, dry skin; infrequent – erythema multiforme, urticaria, acute febrile neutrophilic dermatosis, toxic skin rash, toxic epidermal necrolysis, Stevens-Johnson syndrome, dermatitis, altered hair structure, petechiae, ecchymosis, skin lesions, purpura, skin growths, psoriasis, hyperhidrosis, night sweats, bedsores, acne, blisters, skin pigmentation disorders; rare – skin reactions, Jessner’s lymphocytic infiltration, palmar and plantar erythrodisesthesia, subcutaneous bleeding, reticular lividity, skin induration, papule, photosensitivity reactions, seborrhea, cold sweats, unspecified skin lesions, erythrosis, skin ulcers, nail lesions.

Musculoskeletal and connective tissue disorders: very common – musculoskeletal pain; common – muscle cramps, limb pain, muscle weakness; infrequent – muscle twitching, joint swelling, arthritis, joint stiffness, myopathy, feeling of heaviness; Rarely – rhabdomyolysis, temporomandibular joint syndrome, fistula, joint effusion, pain in jaw, bone disorders, infections and inflammation of musculoskeletal and connective tissue, synovial cysts.

Kidney and urinary tract disorders: often – impaired renal function; infrequent – acute renal failure, chronic renal failure, urinary tract infections, urinary tract complaints, hematuria, urinary retention, urinary disorders, proteinuria, azotemia, oliguria, pollakiuria; rarely – bladder irritation.

Genital organs and the breast: infrequent – vaginal bleeding, pain in the genitals, erectile dysfunction; rarely – testicular dysfunction, prostatitis, breast dysfunction, pain in the testicles, epididymitis, pain in the pelvis, vulvar ulceration.

General disorders and disorders due to the method of administration: very often – pyrexia, increased fatigue, asthenia; often – edema (including peripheral). Peripheral edema, chills, pain, discomfort; infrequent – general physical deterioration, facial edema, injection site reactions, mucous membrane disorders, chest pain, gait disturbance, feeling cold, extravasation, complications from catheter use, change in thirst, discomfort in chest area, feeling of body temperature change, pain at injection site; rare – death (including sudden death) of the injecting drug. death (including sudden), multiple organ failure, bleeding at the insertion site, hernia, impaired healing, inflammation, phlebitis at the insertion site, soreness, ulceration, irritability, noncardiac chest pain, pain at the insertion site, sensation of a foreign body.

Changes of laboratory parameters: frequently – weight loss; infrequently – hyperbilirubinemia, changes in protein parameters, weight gain, changes in blood values, increased concentration of C-reactive protein; rarely – changes in blood gas content, changes in cardiogram (including QT waveform.

Trendy: change in blood gases, changes in cardiogram (including QT-wave magnification), changes in prothrombin time, decreased pH of gastric juice, increased platelet aggregation, increased concentration of troponin I, detection of viruses and changes in serology, changes in urinalysis.

Injuries, intoxications and complications of manipulations: infrequent – falls, contusions; rare – transfusion reactions, fractures, stiffness, facial injuries, joint injuries, burns, lacerations, pain during the procedure, radiation exposure.

Surgical and therapeutic manipulations: rarely – activation of macrophages.

Congenital, hereditary and genetic disorders: rarely – aplasia, GI malformation, ichthyosis.

Patients with mantle cell lymphoma

The safety performance of bortezomib in these patients is similar to that of patients with multiple myeloma. Significant differences between the two patient groups were that thrombocytopenia, neutropenia, anemia, nausea, vomiting, and elevated body temperature were seen more frequently in patients with multiple myeloma compared to patients with mantle cell lymphoma, and peripheral neuropathy, rash, and pruritus were seen more frequently in patients with mantle cell lymphoma.

Overdose

Pregnancy use