The following undesirable phenomena noted when taking Tezal® are distributed according to the frequency of occurrence according to the following gradation: very often (> 10% of cases), often (> 1% to <10%), infrequently (> 0,1 % to <1%), rarely (from> 0.01% to <0.1%) and very rarely (<0.01%).
The newly diagnosed multiform pili glioblastoma (adult patients) Combined phase of treatment (with radiotherapy)
On the part of mechanisms of resistance to infections:
often: candidiasis of the oral cavity, herpes simplex, pharyngitis, wound infection, other infection.
From the side of the blood and lymphatic system:
often: leukopenia, lymphopenia, neutropenia, thrombocytopenia;
infrequently: anemia, febrile neutropenia.
From the cardiovascular system: often: swelling, including legs, hemorrhage;
infrequent: a feeling of heartbeat, increased blood pressure, cerebral hemorrhage.
On the part of the respiratory system: often: cough, shortness of breath;
infrequently: pneumonia, upper respiratory tract infection, nasal congestion.
From the endocrine system: infrequently: the Itenko-Cushing syndrome.
From the skin and subcutaneous fat, breast: very common: alopecia, rash;
often: dermatitis, dry skin, erythema, skin itching, face swelling;
infrequently: photosensitivity reactions, pigmentation disorders, exfoliation.
From the nervous system: very often: headache;
often: anxiety, emotional lability, insomnia, dizziness, aphasia, balance disorder, impaired concentration, confusion and decreased consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, tremor;
infrequently: agitation, apathy, behavioral disorders, depression, hallucinations, impaired perception, extrapyramidal disorders, dysphasia, ataxia, violation gait, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, peripheral neuropathy, parosmia, thirst.
From the musculoskeletal system: often: argalgia, muscle weakness;
infrequently: back pain, musculoskeletal pain, myalgia, myopathy.
From the side of the organ of vision: often: blurred vision;
infrequently: pain in the eyes, gmiaanopsy, visual impairment, decreased visual acuity, limitation of visual fields.
From the genitourinary system:
Frequent: frequent urination, urinary incontinence;
infrequently: impotence.
From the organ of hearing and the vestibular system: often: hearing impairment;
infrequently: pain in the ears, hyperacia, ringing in the ears, otitis media.
From the digestive system. very often: anorexia, constipation, nausea, vomiting;
often: increased activity of alanine aminotransferase, hyperglycemia, weight loss, abdominal pain, stomatitis, diarrhea, dyspepsia, dysphagia, impaired taste; infrequently: hypokalemia,increased alkaline phosphatase activity, weight gain, discoloration of the tongue, increased activity of gamma-glutamyltransferase, aspartate aminotransferase, liver enzymes.
On the part of the body as a whole: very often: fatigue;
often: fever, pain syndrome, radiation damage, allergic reaction; infrequently: "hot flashes" of heat to the body, asthenia, worsening of the condition, chills.
Adjuvant phase of treatment
On the part of mechanisms of resistance to infections:
often: candidiasis of the oral mucosa, another infection;
infrequently: herpes simplex, herpes zoster, influenza-like syndrome.
From the side of the blood and lymphatic system:
often: anemia, febrile neutropenia, leukopenia, thrombocytopenia; infrequently: lymphopenia, petechiae.
From the cardiovascular system:
often: swelling of the legs, hemorrhage, deep vein thrombosis;
infrequently: edema, including peripheral, pulmonary embolism.
On the part of the respiratory system: often: cough, shortness of breath;
infrequently: pneumonia, infection of the upper respiratory tract, sinusitis, bronchitis.
From the endocrine system: infrequently: the Itenko-Cushing syndrome.
From the skin and subcutaneous fat, breast: very common: alopecia, rash; often: dry skin, itching of the skin;
infrequently: erythema, a violation of pigmentation, increased sweating, pain in the breast, swelling of the face.
From the nervous system: very often: headache, convulsions;
often: anxiety, depression, emotional lability, insomnia,
dizziness, aphasia, imbalance, impaired concentration, confusion, dysphasia, speech disorder, hemiparesis, memory impairment, neurological disorders (unspecified), neuropathy, peripheral neuropathy, paresthesia, tremor, drowsiness;
infrequently: hallucinations, ataxia, impaired coordination, amnesia, gait disorders, hemiplegia, hyperesthesia, impaired sensory organs.
From the side of the musculoskeletal system.
often: arthralgia, musculoskeletal pain, myalgia, muscle weakness; infrequently: back pain, myopathy.
From the side of the organ of vision:
often: blurred vision, diplopia, limitation of visual fields; infrequently: pain in the eyes, dry eyes, reduced visual acuity.
From the genitourinary system: often: urinary incontinence;
infrequently: dysuria, amenorrhea, menorrhagia, vaginal bleeding, vaginitis.
From the side of the hearing and vestibular system: often: hearing impairment, ringing in the ears; infrequently: deafness, pain in the ears, verge.
From the digestive system: very often: anorexia, constipation, nausea, vomiting;
often: increased activity of alanine aminotransferase, weight loss, diarrhea, dyspepsia, dysphagia, stomatitis, dryness of the oral mucosa, taste distortion;
infrequently: hyperglycemia, weight gain, bloating, fecal incontinence, hemorrhoids, gastroenteritis, dental diseases, gastrointestinal-factor disorders.
On the part of the body as a whole: very often: fatigue;
often: fever, pain syndrome, radiation damage, allergic reaction; infrequently: asthenia, worsening of the condition, chills.
Laboratory indicators
Myelosuppression (neutropenia and thrombocytopenia) is a dose-limiting side effect. Among patients in both groups (combined and adjuvant therapy), neutrophil changes, including neutropenia, were noted in 8% of cases, and platelet counts, including thrombocytopenia, in 14% of cases.
Progressive or recurrent malignant glioma (adults and children over 3 years old) or malignant melanoma (adults)
On the part of the hematopoiesis system:
very often: thrombocytopenia, neutropenia, lymphopenia;
often: pancytopenia, leukopenia, anemia.
In patients with glioma and metastatic melanoma, thrombocytopenia and grade 3 or 4 neutropenia were noted in 19% and 17%, respectively, in glioma and 20% and 22%, respectively, in melanoma. Hospitalization of the patient and / or removal of temozolomide, moreover, was required in 8% and 4% of cases, respectively, in glioma and in 3% and 1.3% in melanoma. The bone marrow depression developed usually during the first few treatment cycles with a maximum between 21 and 28 days, the recovery usually occurred within 1-2 weeks. No evidence of cumulative myelosuppression was noted.
On the part of the digestive system:
very often: nausea, vomiting, constipation, anorexia.
often: diarrhea, abdominal pain, indigestion, taste perversion. The most frequent were nausea and vomiting. In most cases, these phenomena were 1-2 (from mild to moderate) degree of severity and passed independently or were easily controlled by standard anti-rheumatic therapy. Frequency of severe nausea and vomiting - 4%.
From the nervous system: very often: headache;
often: drowsiness, dizziness, paresthesia, asthenia, pain syndrome.
From the skin and subcutaneous fat:
often: rash, itching, alopecia, petechiae;
very rarely: urticaria, exanthema, erythroderma.
Other:
very often: increased fatigue;
often: weight loss, shortness of breath, fever, chills, general malaise;
rarely: opportunistic infections, including pneumonia; very rarely: angioedema.
Post-registration research data
During postmarketing studies, very often there was a multiform erythema, toxic epidermal necrolysis, Stevens-Johnson syndrome, as well as allergic reactions, including anaphylaxis.
There have been reports of hepatotoxicity, including increased activity of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis. Very rarely there were violations of the liver, including cases with a fatal outcome.
Opportunistic infections were rare, including pneumonia caused by Pneumocystis carnii, very rarely reported cases of interstitial pneumonitis and pneumonitis, as well as pulmonary fibrosis.Also, the development of myelodysplastic syndrome (MDS) and secondary malignant processes, including leukemia, was very rarely observed, and development of prolonged pancytopenia was very rare. Perhaps the development of aplastic anemia, which in a few cases led to a fatal outcome.