Temozolomide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of temozolomide.
Drugs List
Therapeutic Indications
Uses
Malignant glioma showing recurrence or progression
Newly diagnosed glioblastoma multiforme with radiotherapy in adults
Treatment of newly diagnosed glioblastoma multiforme used concomitantly with radiotherapy and subsequently as monotherapy treatment in adults.
Treatment of malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy, in adults and children aged 3 years or older.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Newly diagnosed glioblastoma multiforme
Administer in combination with focal radiotherapy followed by up to 6 cycles of temozolomide monotherapy.
Concomitant phase - temozolomide with focal radiotherapy:
75mg/square metre once daily for 42 days concomitant with focal radiotherapy (60Gy administered in 30 fractions).
Monotherapy phase - following completion of radiotherapy:
4 weeks after completing treatment with temozolomide and radiotherapy, temozolomide should be administered as monotherapy for up to 6 cycles.
Cycle 1: 150mg/square metre once daily for 5 days followed by a 23 day treatment-free interval.
Cycles 2 to 6: 200mg/square metre once daily for 5 days followed by a 23 day treatment-free interval.
Recurrent or progressive malignant glioma
Patients previously untreated with chemotherapy:
All cycles: 200mg/square metre once daily for 5 days followed by a 23 day treatment-free interval.
Patients previously treated with chemotherapy:
Cycle 1: 150mg/square metre once daily for 5 days followed by a 23 day treatment-free interval.
Subsequent cycles: 200mg/square metre once daily for 5 days followed by a 23 day treatment-free interval.
Children
Experience in the use of temozolomide in children is limited. Recurrent or progressive malignant glioma
Children aged 3 years or older: (See Dosage; Adults) Children less than 3 years of age: There is currently no clinical experience with the use of temozolomide in children under the age of 3 years and use in this age group is therefore not recommended.
Additional Dosage Information
Dose modifications for temozolomide with focal radiotherapy
Absolute neutrophil count (ANC) between 0.5 and 1.5 x 10 to the power of 9 per litre or thrombocyte count between 10 and 100 x 10 to the power of 9 per litre:
Interrupt treatment. Repeat full blood counts weekly. Restart treatment once ANC greater than or equal to 1.5 x 10 to the power of 9 per litre and thrombocyte count greater than or equal to 100 x 10 to the power of 9 per litre. No dose modifications required.
ANC below 0.5 x 10 to the power of 9 per litre or thrombocyte count below 10 x 10 to the power of 9 per litre:
Discontinue treatment.
Common toxicity criteria (CTC) non-haematological toxicity grade 2 (excluding alopecia, nausea and vomiting):
Interrupt treatment. Restart when toxicity improves to grade 1 or less. No dose modifications required.
CTC non-haematological toxicity grade 3 or more (excluding alopecia, nausea and vomiting):
Discontinue treatment.
Dose modifications for temozolomide monotherapy
ANC less than 1 x 10 to the power of 9 per litre or thrombocyte count less than 50 x 10 to the power of 9 per litre:
Reduce by one dose level (see below).
If toxicity recurs, at each instance reduce by a further dose level. If the lowest dose level still results in unacceptable toxicity, discontinue treatment.
CTC non-haematological toxicity grade 3 (excluding alopecia, nausea and vomiting):
Reduce by one dose level (see below).
If the same grade 3 toxicity recurs despite dose reduction, discontinue treatment.
If different grade 3 toxicities occur, at each instance reduce by a further dose level. If the lowest dose level still results in grade 3 toxicities occurring, discontinue treatment.
CTC non-haematological toxicity grade 4 (excluding alopecia, nausea and vomiting):
Discontinue treatment.
Dose level reductions:
Where dose reductions are indicated, select the level below the current prescribed dose e.g. currently prescribed 200mg per square metre per day, reduce the dose to 150mg per square metre per day.
If toxicity still occurs at the lowest dose level, discontinue treatment.
Dose level 1: 200mg per square metre per day.
Dose level 0: 150mg per square metre per day.
Dose level -1: 100mg per square metre per day.
Contraindications
Children under 3 years
Breastfeeding
Galactosaemia
Pregnancy
Severe myelosuppression
Precautions and Warnings
Children aged 3 to 18 years
Cytomegalovirus infection
Neutrophil count below 1.5 x 10 to the power of 9 / L
Patients over 70 years
Platelet count below 100 x 10 to the power of 9/ L
Glucose-galactose malabsorption syndrome
Hepatitis B
Lactose intolerance
Renal impairment
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Prophylaxis against Pneumocystis carinii pneumonia is required
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Advise patient to take on an empty stomach 1 hr before or 2 hrs after food
Avoid contact of powder with skin and mucous membranes
Capsules should not be opened or crushed
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform liver function tests before commencing therapy and during therapy
Monitor and manage cytomegalovirus reactivation during treatment
Monitor for and manage hepatitis reactivation during treatment
Monitor full blood counts weekly
Consider the use of anti-emetics before and during therapy
Risk of developing opportunistic infections
Risk of myelodysplastic syndrome and secondary malignancies
Female: Contraception required during and for 6 months after treatment
Male: Contraception required during and for 3 months after treatment
Anti-emetic prophylaxis is recommended in newly diagnosed glioblastoma multiforme, during the concomitant phase (prior to the initial temozolomide dose) and during the monotherapy phase (throughout each treatment cycle).
Anti-emetic therapy may be required in recurrent or progressive malignant glioma, for patients who have experienced severe (grade 3 or 4) vomiting in previous cycles.
Provide prophylaxis against Pneumocystis jirovecii pneumonia (PCP) to all patients receiving concomitant temozolomide and radiotherapy, regardless of lymphocyte count. If lymphopenia occurs, continue prophylaxis until lymphopenia recovers to grade 1 or less. Closely observe all patients, but particularly those receiving steroids, for the development of PCP. PCP is more common in patients receiving temozolomide for longer periods.
Monitor patients for signs of hepatitis, as cases of hepatitis B virus reactivation have been reported. Use of temozolomide in patients with positive hepatitis B serology should be undertaken in conjunction with a hepatologist.
Assess hepatic function prior to initiation, at day 21 during any concomitant therapy and at the end of each cycle during monotherapy. If serious liver toxicity occurs, decision to continue should be based on benefits versus risks. Hepatic toxicity may occur several weeks after treatment is discontinued.
Perform full blood counts prior to initiation, weekly during any concomitant therapy and on day 22 of each cycle during monotherapy. Delay treatment initiation if ANC less than 1.5 x 10 to the power of 9 per litre or thrombocyte count less than 100 x 10 to the power of 9 per litre. If myelosuppression occurs during treatment, interruptions, dose reductions or discontinuation may be required (see Dosage; Additional Dose Information).
Pregnancy and Lactation
Pregnancy
Temozolomide is contraindicated during pregnancy.
The manufacturers recommend that temozolomide is not administered during pregnancy.
There are no studies in pregnant women. In preclinical studies in animals, teratogenicity and/or foetal toxicity were demonstrated. It is considered likely that both temozolomide and the primary metabolite MTIC could cross the placenta.
Lactation
Temozolomide is contraindicated during breastfeeding.
The manufacturers recommend that breastfeeding is discontinued during temozolomide treatment.
It is not known if temozolomide is excreted in breast milk. However, the molecular weight and low plasma protein binding suggest it will be excreted into breast milk.
Counselling
Advise patients the capsules should be given on an empty stomach and swallowed whole with a glass of water.
Advise patients if vomiting occurs after the dose is taken, a second dose should not be taken that day.
Provide pre-treatment counselling on potential effects on fertility including discussing the option of sperm cryopreservation for male patients.
Advise female patients to ensure adequate contraception during treatment and for 6 months after treatment is discontinued.
Advise male patients to ensure adequate contraception during treatment and for 3 months after treatment is discontinued.
Side Effects
Abdominal distension
Agitation
Alopecia
Amenorrhoea
Anaemia
Angioedema
Anorexia
Anxiety
Apathy
Asthenia
Ataxia
Behavioural disturbances
Bronchitis
Candidiasis (mouth or throat)
Cerebral haemorrhage
Cholestasis
Confusion
Convulsions
Cough
Cushingoid changes
Deep vein thrombosis (DVT)
Depression
Diabetes insipidus
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dyspepsia
Dysphagia
Dyspnoea
Ear disorder
Emotional lability
Faecal incontinence
Fatigue
Febrile neutropenia
Fever
Flushing
Gait abnormality
Gastro-intestinal symptoms
Haemorrhage
Haemorrhoids
Hallucinations
Headache
Hemiparesis
Hepatitis
Herpes simplex
Herpes zoster
Herpetic meningoencephalitis
Hyperbilirubinaemia
Hyperglycaemia
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypokalaemia
Impaired concentration
Impaired memory
Impotence
Increased susceptibility to infection
Increases in hepatic enzymes
Insomnia
Leukopenia
Loss of balance
Lymphopenia
Malaise
Menorrhagia
Muscle weakness
Myopathy
Nasal congestion
Nausea
Neurological disorders
Neuropathy
Neutropenia
Oedema
Opportunistic infections
Otitis media
Pain
Palpitations
Pancytopenia
Paraesthesia
Parosmia
Petechiae
Pharyngitis
Precipitation of status epilepticus
Pulmonary embolism
Reactivation of infection
Rigors
Sensory disturbances
Sinusitis
Skin reactions
Somnolence
Speech disturbances
Stomatitis
Taste disturbances
Thrombocytopenia
Tongue discolouration
Tremor
Urinary abnormalities
Vaginitis
Vertigo
Visual disturbances
Weight changes
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Temodal Capsules. Merck Sharp & Dohme (UK) Limited. Revised August 2021.
Summary of Product Characteristics: Temozolomide Accord 5mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide Accord 20mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide Accord 100mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide Accord 140mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide Accord 180mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide Accord 250mg hard capsules. Accord Healthcare Limited. Revised September 2019.
Summary of Product Characteristics: Temozolomide 5mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
Summary of Product Characteristics: Temozolomide 20mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
Summary of Product Characteristics: Temozolomide 100mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
Summary of Product Characteristics: Temozolomide 140mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
Summary of Product Characteristics: Temozolomide 180mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
Summary of Product Characteristics: Temozolomide 250mg hard capsules. Ranbaxy (UK) Limited a Sun Pharmaceutical Company. Revised September 2019.
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