Edit the instructions. Bortezomib, in the dosage form of lyophilizate

The need to supplement the instructions for the use of medicines containing bortezomib the following information:

1. In the section "Indications for use" correct "mantle cell leukemia in patients who had previously received at least one line of therapy" for "mantle cell lymphoma."

2. Section "Contraindications" add information on the simultaneous use with strong inductors of the isoenzyme CYP3A (rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's wort pitted).

3. In the section "Mode of administration and dose" in Table 1 in the section on the 1st or 2nd degree of severity of peripheral neuropathy and dose reduction to 1.0 mg / m², supplement "... or change the mode of administration by 1.3 mg / m once a week." It is recommended that the section be supplemented with information on multiple myeloma in previously untreated patients who are not candidates for stem cell transplantation, relapsing multiple myeloma, recommended doses when used in combination with pegylated liposomal doxorubicin when used in combination with dexamethasone, o re-therapy of multiple myeloma, the recommended dose when used in combination with rituximab, cyclophosphamide doxorubicin and prednisone at a previous untreated mantle cell lymphoma.

Infections and infestations:

often - herpes simplex, surrounding herpes (incl.disseminated and ophthalmoherpes), pneumonia, fungal infections;

infectious, bacterial, viral infections, sepsis (including septic shock), bronchopneumonia, herpesvirus infection, herpetic meningoencephalitis, bacteremia (including staphylococcal), barley, influenza, inflammation of subcutaneous fat, 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

Metabolic disorders and eating disorders:

very often - a decrease in appetite; often - dehydration, hypokalemia, hyponatremia, changes in blood glucose concentration, hypocalcemia, changes in enzyme activity;

infrequently - tumor lysis syndrome, lack of weight gain, hypomagnesemia, hypophosphatemia, hyperkalemia, hypercalcemia, hypernatremia, changes in uric acid concentration, diabetes mellitus, fluid retention;

rarely - hypermagnesia, acidosis, disturbance of water-electrolyte balance, excessive accumulation of fluid,hypochloremia, hypovolemia, hyperchloremia, hyperphosphatemia, metabolic disorders, vitamin B deficiency, vitamin B12 deficiency, gout, increased appetite, alcohol intolerance

Impaired nervous system:

very often - neuropathy, peripheral sensory neuropathy, dysesthesia, neuralgia; often - motor neuropathy, loss of consciousness (including fainting), dizziness, taste distortion, lethargy, headache;

infrequent - tremor, peripheral sensorimotor neuropathy, dyskinesia, impaired balance, memory loss (excluding dementia.), encephalopathy, posterior reversible encephalopathy syndrome, neurotoxicity, seizures, post-herpetic neuralgia, speech disorder, a syndrome of "restless legs", migraine, sciatica, impaired concentration attention, pathological reflexes, parosmia;

rarely - intracerebral haemorrhage, intracranial hemorrhage (including subarachnoid), cerebral edema, transient ischemic attack, coma, autonomic nervous system imbalance, autonomic neuropathy, cranial nerve paralysis, paralysis, paresis, pre-occlusive condition, brainstem disease syndrome, violation cerebral circulation,radicular syndrome, psychomotor hyperactivity, spinal cord compression, cognitive disorders, movements disorders of the nervous system, sciatica, excessive salivation, muscle hypotonia

Disorders from the side of the organ of vision:

often - swelling of the eyes, visual impairment, conjunctivitis;

infrequent - eye hemorrhage, eyelid infections, eye inflammation, diplopia, dry eyes, eye irritation, eye pain, increased lacrimation, discharge from the eyes;

rarely - corneal lesion, exophthalmos, retinitis, scotoma, eye damage (including age), dacryoadenitis, photophobia, photopsia, optic neuropathy, different degrees of visual impairment (blindness)

Disturbances from the organ of hearing and balance:

often - vertigo;

infrequent - ringing in the ears, hearing impairment (to deafness), discomfort in the ear;

rarely bleeding, vestibular neuronitis, ear damage

Heart Disease:

infrequently - cardiac tamponade, cardiopulmonary shock, cardiac fibrillation (including atrial fibrillation), heart failure (including left and right ventricles), arrhythmia, tachycardia, palpitations, angina, pericarditis (includingexudative pericarditis), cardiomyopathy, ventricular dysfunction, bradycardia;

rarely - atrial flutter, myocardial infarction, atrioventricular blockade, cardiovascular disorders (including cardiogenic shock), pirouette ventricular tachysystolic type arrhythmia, unstable angina pectoris, heart valve diseases, coronary insufficiency, sinus node arrest

Disorders from the vascular system:

often - lowering blood pressure, orthostatic hypotension, increasing blood pressure;

infrequently, stroke, deep vein thrombosis, bleeding, thrombophlebitis (including superficial), circulatory collapse (including hypovolemic shock), phlebitis, hot flashes, hematoma (including perirenal), decreased peripheral circulation, vasculitis, hyperemia (including ocular);

rarely - embolism of peripheral vessels, lymphedema, pallor, erythromelalgia, vasodilation, change in color of veins, venous insufficiency

Disturbances from the respiratory system, thorax and mediastinum:

often shortness of breath, nosebleeds, upper and lower respiratory tract infections, cough;

infrequent - pulmonary embolism, pleural effusion, pulmonary edema (including acute), pulmonary alveolar hemorrhage, bronchospasm, chronic obstructive pulmonary disease, hypoxemia, airway obstruction, hypoxia, pleurisy, hiccough, rhinorrhea, dysphonia, wheezing;

rarely respiratory failure, acute respiratory distress syndrome, apnea, pneumothorax, atelectasis, pulmonary hypertension, hemoptysis, hyperventilation, orthopnea, pneumonitis, respiratory alkalosis, tachypnea, pulmonary fibrosis, bronchial dysfunction, hypocapnia, interstitial lung disease, pulmonary infiltration, a feeling of tightness in the throat, dryness in the throat, increased secretion in the upper respiratory tract, irritation of the throat, cough syndrome of the upper respiratory tract

Disorders from the gastrointestinal tract:

very often - nausea, vomiting, diarrhea, constipation;

often bleeding from the gastrointestinal tract (including bleeding of the mucous membrane), dyspepsia, stomatitis, a violation of the tone of the gastrointestinal tract, pain in the throat and pharynx, pain in the abdomen (including gastrointestinal pain and pain in the spleen), disorders of the oral cavity, flatulence;

infrequently - pancreatitis (incl.chronic), vomiting of blood, puffiness of the lips, obstruction of the digestive tract (including intestinal obstruction), discomfort in the abdomen, ulceration of the oral mucosa, enteritis, gastritis, bleeding from the gums, gastroesophageal reflux disease, colitis (incl. pseudomembranous colitis), ischemic colitis, inflammation of the mucous membrane of the gastrointestinal tract, dysphagia, irritable bowel syndrome, gastrointestinal disorders, plaque in the tongue, motility disorder of the digestive tract, disorders of the salivary glands;

rarely acute pancreatitis, peritonitis, edema of the tongue, ascites, esophagitis, cheilitis, fecal incontinence, anal sphincter atony, fecaloma, ulceration and perforation of the gastrointestinal tract, gingival hypertrophy, megacolon, rectal discharge, blistering in the throat, pain in the throat lips, periodontitis, anal fissure, change in the rhythm of defecation, procalgia, stool disorders

Disorders of the hepatobiliary system:

often - a change in active "hepatic" enzymes;

infrequently - hepatotoxicity (including liver disorders), hepatitis, cholestasis;

rarely - hepatic insufficiency hepatomegaly, Badda-Chiari syndrome, cytomegalovirus hepatitis, hepatic bleeding, cholelithiasis

Disturbances from the sides of the skin and subcutaneous tissue:

often - a 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 structures, petechia, ecchymosis, skin lesions, purpura, skin tumors, psoriasis, hyperhidrosis, night sweats, lay out acne, blisters, skin pigmentation disorder;

rarely - skin side reactions, Jessner's lymphocytic infiltration, palmar-plantar erythrodysesthesia, subcutaneous bleeding, reticular ledo, skin induration, papule, photosensitivity reactions, seborrhea, cold sweats, skin lesions, erythrosis, skin ulcers, nail damage

Disorders from the musculoskeletal system and connective tissue:

very often - musculoskeletal pain;

often - muscle spasms, pain limbs muscle weakness;

infrequently - muscle twitching, swelling of the joints, arthritis, joint stiffness, myopathy, sensation of heaviness;

rarely - rhabdomyolysis, temporomandibular joint syndrome, fistula joint effusion, pain in the jaw, bone disorders, infections and inflammation of the musculoskeletal and connective tissue, synovial cysts

Disorders from the kidneys and urinary tract:

often - impaired renal function;

infrequently - acute renal failure, chronic renal failure, urinary tract infections, urinary tract side complaints, hematuria, urinary retention, urination disorder, proteinuria, azotemia, oliguria, pollakiuria;

rarely - irritation of the bladder

Violations of the genitals and breast:

infrequently - vaginal bleeding, pain in the genitals, erectile dysfunction;

rarely - dysfunction of the testicles, prostatitis, malfunction of the breast, soreness of the testicles, epididymitis, pain in the pelvic region, ulceration of the vulva

General disorders and disorders due to the method of application:

very often - pyrexia, increased fatigue, asthenia;

often - swelling (including peripheral), chills, pain, discomfort;

infrequent general physical health, facial swelling, reactions at the site of mucosal disruption, chest pain, gait disturbance, cold feeling, extravasation, complications from the use of a catheter, a change in thirst, discomfort in the chest, a feeling of body temperature change , pain at the injection site;

rarely - death (incl.sudden, multichannel insufficiency, bleeding at the injection site, hernia, disruption of healing processes, inflammation, phlebitis at the injection site, tenderness, ulceration, irritability, non-cardiac pain in the chest, pain at the site of insertion of the catheter, foreign body sensation

Changes in laboratory indicators:

often - a decrease in body weight;

infrequently - hyperbilirubinemia, changes in protein indexes, weight gain, changes in blood counts, increased concentration of C-reactive protein;

rarely changes in the content of gases in the blood, changes in the cardiogram (including an increase in the QT wave), changes in prothrombin time, a decrease in the pH of gastric juice, increased platelet aggregation, increased troponin I concentration, virus detection and alteration in serology, changes in urine analysis.

5. In the section "Special instructions" it is recommended to supplement the section on thrombocytopenia / neutropenia. "When used concomitantly with melphalan and prednisolone, when the platelet count is ≤ 30 * 10⁹/ l, drug therapy should be suspended "corrected" Patients with seizures or epilepsy in the anamnesis described infrequent cases of convulsions "on" convulsions.In patients with no seizures or epilepsy, an anamnesis describes infrequent cases of seizures. "