The following undesirable phenomena noted with the administration of temozolomide are distributed according to the frequency of occurrence according to the following gradation: very often (> 10% of cases), often (> 1% to <10%), infrequently (from> 0.1% to <1%), rarely (from> 0.01% to <0.1%) and very rarely (<0.01%).
The newly discovered multiform glioblastoma (adult patients)
Combined phase of treatment (with radiotherapy)
On the part of mechanisms of resistance to infections
Purely: candidiasis of the oral mucosa, herpes simplex, pharyngitis, wound infection, other infection.
On the part of the blood and lymphatic system
Often: leukopenia, lymphopenia, neutropenia, thrombocytopenia;
Infrequently: anemia, febrile neutropenia.
From the side of the cardiovascular system
Often: edema, including the legs, hemorrhage;
Infrequently: a feeling of heartbeat, an increase in blood pressure, a hemorrhage into the brain.
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: syndrome Itenko-Cushing.
From the skin and subcutaneous fat, breast
Often: alopecia, rash;
Often: dermatitis, dry skin, erythema, skin itching, face swelling;
Infrequently: photosensitivity reaction, pigmentation disorder, exfoliation.
From the nervous system
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, gait disorders, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, peripheral neuropathies, parasymia, thirst.
From the side of the musculoskeletal system
Often: arthralgia, muscle weakness;
Infrequently: pain in the back, musculoskeletal pain, myalgia, myopathy.
From the side of the organ of vision
Often: blurred vision;
Infrequently: pain in the eyes, hemianopsia, visual impairment, decreased visual acuity, limitation of visual fields.
From the genitourinary system
Often: frequent urination, urinary incontinence;
Infrequently: impotence
From the organs of hearing and vestibular system
Often: hearing impairment;
Infrequently: pain in the ears, hyperacia, ringing in the ears, otitis media.
From the side of the digestive system
Often: anorexia, constipation, nausea, vomiting;
Often: increased alanine aminotransferase activity, hyperglycemia, weight loss, abdominal pain, diarrhea, indigestion, dysphagia, stomatitis, taste disorder;
Infrequently: hypokalemia, increased alkaline phosphatase activity, weight gain, discoloration of the tongue, increased activity of gamma glutamyltransferase, aspartate aminotransferase, liver enzymes.
From the body as a whole
Often: increased fatigue;
Often: fever, pain syndrome, radiation damage, allergic reaction;
Infrequently: "hot flushes" 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.
On the part of the blood and lymphatic system
Often: anemia, febrile neutropenia, leukopenia, thrombocytopenia;
Infrequently: lymphopenia, petechiae.
From the side of the cardiovascular system
Often: edema 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, upper respiratory tract infection, sinusitis, bronchitis.
From the endocrine system
Infrequently: syndrome Itenko-Cushing.
From the skin and subcutaneous fat, breast
Often: alopecia, rash;
Often: dry skin, itching of the skin;
Infrequently: erythema, impaired pigmentation, excessive sweating, pain in the breast, swelling of the face.
From the nervous system
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, drowsiness, tremor;
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, decreased visual acuity.
From the genitourinary system
Often: urinary incontinence;
Infrequently: dysuria, amenorrhea, menorrhagia. vaginal bleeding, vaginitis.
From the organs of hearing and vestibular system
Often: hearing impairment, ringing in the ears;
Infrequently: deafness, pain in the ears, vertigo.
From the side of the digestive system
Often: anorexia, constipation, nausea, vomiting;
Often: increased activity of alanine aminotransferase, weight loss, diarrhea, dyspepsia, dysphagia, stomatitis, dry mouth, perversion of taste;
Infrequently: hyperglycemia, weight gain, bloating, fecal incontinence, hemorrhoids, gastroenteritis, gastrointestinal disturbances.
From the body as a whole
Often: increased fatigue;
Often: fever, pain syndrome, radiation damage, allergic reaction, dental disorders.
Infrequently: asthenia, worsening of the condition, chills.
Laboratory indicators
Myelosuppression (neutropenia and thrombocytopenia) is a dose-limiting side effect.Among patients of both groups (with combined and adjuvant therapy), changes in levels 3 and 4 on the neutrophil side, 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
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 was required in 8% and 4% of cases, respectively, for glioma and 3% and 1.3% for melanoma. Oppression of the bone marrow developed usually during the first few cycles of treatment, with a maximum between 21 and 28 days: the recovery occurred, usually within 1-2 weeks. No evidence of cumulative myelosuppression was noted.
From the side of the digestive system
Often: nausea, vomiting, constipation, anorexia;
Often: diarrhea, abdominal pain, dyspepsia, taste perversion. The most frequent were nausea and vomiting. In most cases, these events were 1-2 (mild to moderate) severity and were self-controlled or easily controlled with standard anti-emetic therapy. The frequency of severe nausea and vomiting is 4%.
From the nervous system
Often: headache;
Often: drowsiness, dizziness, paresthesia, asthenia, pain syndrome.
From the skin and subcutaneous fat
Often: rash, itching, alopecia, petechiae;
Rarely: urticaria, exanthema, erythroderma, erythema multiforme.
Other
Often: increased fatigue;
Often: weight loss, shortness of breath, fever, chills, general malaise;
Rarely: opportunistic infections, including pneumocystis pneumonia;
Rarely: angioedema, allergic reactions, including anaphylactic shock.
Post-registration research data
In the course of postmarketing studies with the use of temozolomide in clinical practice, the following undesirable phenomena were noted: very rarely -erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and allergic reactions, including anaphylaxis; pulmonary fibrosis, respiratory failure.
The cases of hepatotoxicity, including increased activity of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis are reported.
Very rarely, when treated with temozolomide, hepatic insufficiency was noted, including fatal cases.
Opportunistic infections were rare, including pneumonia caused by Pneumocystis carinii, as well as the reactivation of infections such as cytomegalovirus and hepatitis B. Very rarely reported cases of interstitial pneumonitis and pneumonitis. Also, very rarely was the development of myelodysplastic syndrome (MDS) and secondary malignant processes, including leukemia; very rarely there was a development of prolonged pancytopenia with a risk of developing aplastic anemia, which in a few cases led to death. On the part of the endocrine system, there have been cases of development of diabetes insipidus.