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Temodal is a brand name for Temozolomide. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Temodal is indicated for the treatment of: - adult patients with newly-diagnosed glioblastoma multiforme concomitantly with radiotherapy (RT) and subsequently as monotherapy treatment. - children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or…
Verbatim from this product's EMA label. Tap a section to expand.
Temodal should only be prescribed by physicians experienced in the oncological treatment of brain tumours. 4). Posology Adult patients with newly-diagnosed glioblastoma multiforme Temodal is administered in combination with focal radiotherapy (concomitant phase) followed by up to 6 cycles of temozolomide (TMZ) monotherapy (monotherapy phase).
4 Concomitant phase TMZ is administered orally at a dose of 75 mg/m2 daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions). No dose reductions are recommended, but delay or discontinuation of TMZ administration should be decided weekly according to haematological and non-haematological toxicity criteria.
5 x 109/l - thrombocyte count ≥ 100 x 109/l - common toxicity criteria (CTC) non-haematological toxicity ≤ Grade 1 (except for alopecia, nausea and vomiting). During treatment a complete blood count should be obtained weekly. TMZ administration should be temporarily interrupted or permanently discontinued during the concomitant phase according to the haematological and non-haematological toxicity criteria as noted in Table 1.
Table 1. 5 x 109/l; thrombocyte count 100 x 109/l; CTC non-haematological toxicity Grade 1 (except for alopecia, nausea, vomiting). Monotherapy phase Four weeks after completing the TMZ + RT concomitant phase, TMZ is administered for up to 6 cycles of monotherapy treatment.
Dose in Cycle 1 (monotherapy) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment. 5 x 109/l, and the thrombocyte count is ≥ 100 x 109/l. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.
Once escalated, the dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs. Dose reductions and discontinuations during the monotherapy phase should be applied according to Tables 2 and 3.
During treatment a complete blood count should be obtained on Day 22 (21 days after the first dose of TMZ). The dose should be reduced or administration discontinued according to Table 3. Table 2. TMZ dose levels for monotherapy treatment Dose level TMZ dose (mg/m2/day) Remarks –1 100 Reduction for prior toxicity 0 150 Dose during Cycle 1 1 200 Dose during Cycles 2-6 in absence of toxicity 5 Table 3.
0 x 109/l See footnote b Thrombocyte count < 50 x 109/l See footnote b CTC non-haematological Toxicity (except for alopecia, nausea, vomiting) CTC Grade 3 CTC Grade 4b a: TMZ dose levels are listed in Table 2. b: TMZ is to be discontinued if: • dose level -1 (100 mg/m2) still results in unacceptable toxicity • the same Grade 3 non-haematological toxicity (except for alopecia, nausea, vomiting) recurs after dose reduction.
Summary of the safety profile Clinical trial experience In patients treated with TMZ in clinical trials, the most common adverse reactions were nausea, vomiting, constipation, anorexia, headache, fatigue, convulsions, and rash. Most haematologic adverse reactions were reported commonly; the frequency of Grade 3-4 laboratory findings is presented after Table 4.
For patients with recurrent or progressive glioma, nausea (43 %) and vomiting (36 %) were usually Grade 1 or 2 (0 – 5 episodes of vomiting in 24 hours) and were either self-limiting or readily controlled with standard anti-emetic therapy.
The incidence of severe nausea and vomiting was 4 %. Tabulated list of adverse reactions Adverse reactions observed in clinical studies and reported from post-marketing use of TMZ are listed in Table 4. These reactions are classified according to System Organ Class and frequency.
Frequency groupings are defined according to the following convention:
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 4. Adverse reactions in patients treated with temozolomide Infections and infestations Common: Infections, herpes zoster, pharyngitisa, candidiasis oral Uncommon: Opportunistic infection (including PCP), sepsis†, meningoencephalitis herpetic†, CMV infection, CMV reactivation, hepatitis B virus†, herpes simplex, infection reactivation, wound infection, gastroenteritisb Neoplasm benign, malignant, and unspecified Uncommon: Myelodysplastic syndrome (MDS), secondary malignancies, including myeloid leukaemia Blood and lymphatic system disorders Common: Febrile neutropenia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, anaemia Uncommon: Prolonged pancytopenia, aplastic anaemia†, pancytopenia, petechiae Immune system disorders Common: Allergic reaction 10 Table 4.
8). Meningoencephalitis herpetic In post marketing cases, meningoencephalitis herpetic (including fatal cases) has been observed in patients receiving TMZ in combination with radiotherapy, including cases of concomitant steroids administration.
Pneumocystis jirovecii pneumonia Patients who received concomitant TMZ and RT in a pilot trial for the prolonged 42-day schedule were shown to be at particular risk for developing Pneumocystis jirovecii pneumonia (PCP). Thus, prophylaxis against PCP is required for all patients receiving concomitant TMZ and RT for the 42-day regimen (with a maximum of 49 days) regardless of lymphocyte count.
If lymphopenia occurs, they are to continue the prophylaxis until recovery of lymphopenia to grade ≤ 1. There may be a higher occurrence of PCP when TMZ is administered during a longer dosing regimen. However, all patients receiving TMZ, particularly patients receiving steroids, should be observed closely for the development of PCP, regardless of the regimen.
Cases of fatal respiratory failure have been reported in patients using TMZ, in particular in combination with dexamethasone or other steroids. HBV Hepatitis due to hepatitis B virus (HBV) reactivation, in some cases resulting in death, has been reported.
Experts in liver disease should be consulted before treatment is initiated in patients with positive hepatitis B serology (including those with active disease). During treatment patients should be monitored and managed appropriately.
8). Baseline liver function tests should be performed prior to treatment initiation. If abnormal, physicians should assess the benefit/risk prior to initiating temozolomide including the potential for fatal hepatic failure. For patients on a 42 day treatment cycle liver function tests should be repeated midway during this cycle.
For all patients, liver function tests should be checked after each treatment cycle. For patients with significant liver function abnormalities, physicians should assess the benefit/risk of continuing treatment. Liver toxicity may occur several weeks or more after the last treatment with temozolomide.
1. Hypersensitivity to dacarbazine (DTIC). 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Adult and paediatric patients 3 years of age or older with recurrent or progressive malignant glioma: A treatment cycle comprises 28 days. In patients previously untreated with chemotherapy, TMZ is administered orally at a dose of 200 mg/m2 once daily for the first 5 days followed by a 23 day treatment interruption (total of 28 days).
4) Special populations Paediatric population In patients 3 years of age or older, TMZ is only to be used in recurrent or progressive malignant glioma. 1). The safety and efficacy of TMZ in children under the age of 3 years have not been established.
No data are available. Patients with hepatic or renal impairment The pharmacokinetics of TMZ were comparable in patients with normal hepatic function and in those with mild or moderate hepatic impairment. No data are available on the administration of TMZ in patients with severe hepatic impairment (Child’s Class C) or with renal impairment.
Based on the pharmacokinetic properties of TMZ, it is unlikely that dose reductions are required in patients with severe hepatic impairment or any degree of renal impairment. However, caution should be exercised when TMZ is administered in these patients.
Elderly patients Based on a population pharmacokinetic analysis in patients 19-78 years of age, clearance of TMZ is not affected by age. 4). Method of administration Temodal hard capsules should be administered in the fasting state. The capsules must be swallowed whole with a glass of water and must not be opened or chewed.
If vomiting occurs after the dose is administered, a second dose should not be administered that day. 6
Adverse reactions in patients treated with temozolomide Uncommon:
Anaphylaxis Endocrine disorders Common: Cushingoidc Uncommon: Diabetes insipidus Metabolism and nutrition disorders Very common: Anorexia Common: Hyperglycaemia Uncommon: Hypokalaemia, alkaline phosphatase increased Psychiatric disorders Common: Agitation, amnesia, depression, anxiety, confusion, insomnia Uncommon: Behaviour disorder, emotional lability, hallucination, apathy Nervous system disorders Very common: Convulsions, hemiparesis, aphasia/dysphasia, headache Common: Ataxia, balance impaired, cognition impaired, concentration impaired, consciousness decreased, dizziness, hypoesthesia, memory impaired, neurologic disorder, neuropathyd, paraesthesia, somnolence, speech disorder, taste perversion, tremor Uncommon: Status epilepticus, hemiplegia, extrapyramidal disorder, parosmia, gait abnormality, hyperaesthesia, sensory disturbance, coordination abnormal Eye disorders Common: Hemianopia, vision blurred, vision disordere, visual field defect, diplopia, eye pain Uncommon: Visual acuity reduced, eyes dry Ear and labyrinth disorders Common: Deafnessf, vertigo, tinnitus, earacheg Uncommon: Hearing impairment, hyperacusis, otitis media Cardiac disorders Uncommon: Palpitation Vascular disorders Common: Haemorrhage, embolism pulmonary, deep vein thrombosis, hypertension Uncommon: Cerebral haemorrhage, flushing, hot flushes Respiratory, thoracic and mediastinal disorders Common: Pneumonia, dyspnoea, sinusitis, bronchitis, coughing, upper respiratory infection Uncommon: Respiratory failure†, interstitial pneumonitis/pneumonitis, pulmonary fibrosis, nasal congestion Gastrointestinal disorders Very common: Diarrhoea, constipation, nausea, vomiting Common: Stomatitis, abdominal painh, dyspepsia, dysphagia 11 Table 4.
Adverse reactions in patients treated with temozolomide Uncommon:
Abdominal distension, faecal incontinence, gastrointestinal disorder, haemorrhoids, mouth dry Hepatobiliary disorders Uncommon: Hepatic failure†, hepatic injury, hepatitis, cholestasis, hyperbilirubinemia Skin and subcutaneous tissue disorders Very Common: Rash, alopecia Common: Erythema, dry skin, pruritus Uncommon: Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, erythroderma, skin exfoliation, photosensitivity reaction, urticaria, exanthema, dermatitis, sweating increased, pigmentation abnormal Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Common: Myopathy, muscle weakness, arthralgia, back pain, musculoskeletal pain, myalgia Renal and urinary disorders Common: Micturition frequency, urinary incontinence Uncommon: Dysuria Reproductive system and breast disorders Uncommon: Vaginal haemorrhage, menorrhagia, amenorrhoea, vaginitis, breast pain, impotence General disorders and administration site conditions Very common: Fatigue Common: Fever, influenza-like symptoms, asthenia, malaise, pain, oedema, oedema peripherali Uncommon: Condition aggravated, rigors, face oedema, tongue discolouration, thirst, tooth disorder Investigations Common: Liver enzymes elevationj, weight decreased, weight increased Uncommon: Gamma-glutamyltransferase increased Injury, poisoning and procedural complications Common: Radiation injuryk a Includes pharyngitis, nasopharyngeal pharyngitis, pharyngitis Streptococcal b Includes gastroenteritis, gastroenteritis viral c Includes cushingoid, Cushing syndrome d Includes neuropathy, peripheral neuropathy, polyneuropathy, peripheral sensory neuropathy, peripheral motor neuropathy e Includes visual impairment, eye disorder f Includes deafness, deafness bilateral, deafness neurosensory, deafness unilateral g Includes earache, ear discomfort h Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal discomfort i Includes oedema peripheral, peripheral swelling j Includes liver function test increased, alanine […]
8). 7 Anti-emetic therapy Nausea and vomiting are very commonly associated with TMZ. Anti-emetic therapy may be administered prior to or following administration of TMZ. Adult patients with newly-diagnosed glioblastoma multiforme Anti-emetic prophylaxis is recommended prior to the initial dose of concomitant phase and it is strongly recommended during the monotherapy phase.
Patients with recurrent or progressive malignant glioma Patients who have experienced severe (Grade 3 or 4) vomiting in previous treatment cycles may require anti-emetic therapy. Laboratory parameters Patients treated with TMZ may experience myelosuppression, including prolonged pancytopenia, which may result in aplastic anaemia, which in some cases has resulted in a fatal outcome.
In some cases, exposure to concomitant medicinal products associated with aplastic anaemia, including carbamazepine, phenytoin, and sulfamethoxazole/trimethoprim, complicates assessment. 5 x 109/l and platelet count 100 x 109/l. 5 x 109/l and platelet count > 100 x 109/l.
2). Dose levels include 100 mg/m2, 150 mg/m2, and 200 mg/m2. The lowest recommended dose is 100 mg/m2. Paediatric population There is no clinical experience with use of TMZ in children under the age of 3 years. 1). Elderly patients (> 70 years of age) Elderly patients appear to be at increased risk of neutropenia and thrombocytopenia, compared with younger patients.
Therefore, special care should be taken when TMZ is administered in elderly patients. Female patients Women of childbearing potential have to use effective contraception to avoid pregnancy while they are receiving TMZ, and for at least 6 months following completion of treatment.
6). Lactose This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. 8 Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.