Temozolomide

Registered South African indications:

• Newly diagnosed glioblastoma multiforme after debulking surgery
• Recurrent malignant glioma such as glioblastoma multiforme or anaplastic astrocytoma
• Advanced metastatic malignant melanoma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to dacarbazine
• Severe myelosuppression

Cautions

• Pregnancy
• Breastfeeding
• Males and females of reproductive potential
• Renal impairment
• Severe hepatic impairment
• Elderly
• Longer dosing regimens
• Patients with positive hepatitis B serology 
• Patients with latent CMV infections
• Severe vomiting in previous treatment cycles
• Children <3 years
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap

Used for the treatment of

• Newly-diagnosed glioblastoma multiforme after debulking surgery concomitantly with radiotherapy and subsequently as monotherapy or adjuvant treatment
• Recurrent or progressive malignant glioma such as glioblastoma multiforme or anaplastic astrocytoma after standard therapy
• Advanced metastatic malignant melanoma

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Consult specialist for dosages and regimens

Paed. forms avail. In SA and covered in this monograph: cap

Used for the treatment of

• Recurrent or progressive malignant glioma such as glioblastoma multiforme or anaplastic astrocytoma after standard therapy

Younger than 3 years

• Not established for use

Older than 3 years

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Consult specialist for dosages and regimens

Pregnancy

• Caution
• There is no data in pregnant women. In preclinical studies in rats and rabbits receiving 150mg/m², teratogenicity and/or foetal toxicity were demonstrated
• Temozolomide should not be administered to pregnant women. Women of childbearing potential should be advised to use effective contraception to avoid pregnancy while they are receiving temozolomide
• If use during pregnancy must be considered, the patient should be apprised of the potential risk to the foetus

Breastfeeding

• Caution; not recommended
• It is not known whether temozolomide is excreted in human milk; thus, breastfeeding should be discontinued while receiving treatment with temozolomide

Fertility

• Temozolomide can have genotoxic effects. Therefore, men being treated with it should be advised not to father a child up to 6 months after receiving the last dose and to seek advice on cryoconservation of sperm prior to treatment, because of the possibility of irreversible infertility due to therapy with temozolomide

Renal Impairment

• Caution; no information available
  Based on the pharmacokinetic properties of temozolomide, it is unlikely that dose reductions are required in patients with any degree of renal impairment. However, caution should be exercised when administered in these patients

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  Based on the pharmacokinetic properties of temozolomide, it is unlikely that dose reductions are required in patients with severe hepatic impairment. However, caution should be exercised when administered in these patients

Elderly            

• Caution; no dose adjustment recommended
  Patients >70 years may be at increased risk of neutropenia and thrombocytopenia

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Depression
• Emotional lability
• Insomnia
• Agitation
• Apathy
• Behaviour disorder
• Depression
• Hallucination
• Amnesia
• Headache
• Seizures
• Decreased consciousness
• Somnolence
• Impaired balance
• Dizziness
• Confusion
• Impaired memory
• Neurologic disorder
• Impaired concentration
• Neuropathy
  - Peripheral neuropathy
  - Polyneuropathy
  - Peripheral sensory neuropathy
  - Peripheral motor neuropathy
• Paresthesia
• Speech disorder
• Tremor
• Hemiparesis
• Aphasia/dysphasia
• Peripheral neuropathy
• Status epilepticus
• Extrapyramidal disorder
• Hemiparesis
• Ataxia
• Impaired cognition
• Abnormal gait
• Hyperaesthesia
• Hypoaesthesia
• Hemiplegia
• Abnormal coordination
• Fatigue

Cardiovascular Disorders

• Palpitation
• Haemorrhage
• Deep venous thrombosis
• Cerebral haemorrhage
• Hypertension
• Pulmonary embolism
• Hot flushes
• Oedema
  - Peripheral oedema
  - Peripheral swelling
  - Face oedema

Respiratory Disorders

• Dyspnoea
• Cough
• Pneumonia
• Upper respiratory infection
• Nasal congestion
• Sinusitis
• Bronchitis
• Interstitial pneumonitis/pneumonitis
• Pulmonary fibrosis
• Respiratory failure (including fatal outcome)

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting
• Stomatitis
• Diarrhoea
• Abdominal pain
  - Lower abdominal pain
  - Upper abdominal pain
  - Abdominal discomfort
• Dysphagia
• Dyspepsia
• Dry mouth
• Abdominal distension
• Faecal incontinence
• Haemorrhoids
• Tongue discolouration
• Tooth disorder

Hepatobiliary Disorders

• Increased hepatic enzymes
  - Increased alanine aminotransferase
  - Increased aspartate aminotransferase
• Increased gamma-glutamyltransferase
• Hepatic failure (including fatal outcome)
• Hepatic injury
• Hepatitis
• Cholestasis
• Hyperbilirubinemia

Genitourinary Disorders

• Micturition frequency
• Urinary incontinence
• Dysuria
• Impotence
• Vaginal haemorrhage
• Menorrhagia
• Amenorrhea
• Vaginitis
• Breast pain

Endocrine and Metabolic Disorders

• Cushingoid appearance
• Cushing's syndrome
• Diabetes insipidus
• Anorexia
• Hyperglycaemia
• Decreased weight
• Hypokalemia
• Increased alkaline phosphatase
• Increased weight  
• Thirst

Musculoskeletal Disorders

• Muscle weakness
• Arthralgia
• Musculoskeletal pain
• Myalgia
• Myopathy
• Back pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Alopecia
• Dermatitis
• Dry skin
• Erythema
• Pruritus
• Skin exfoliation
• Photosensitivity reaction
• Urticaria
• Dermatitis
• Exanthema
• Abnormal pigmentation 
• Erythema multiforme
• Erythroderma
• Abnormal pigmentation
• Increased sweating
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Flushing
• Angioedema
• Drug reaction with eosinophilia and systemic symptoms

Immune, Blood and Lymphatic System Disorders

• Infection
• Herpes zoster
• Pharyngitis
  - Nasopharyngeal pharyngitis
  - Streptococcal pharyngitis
• Oral candidiasis
• Opportunistic infection
• Pneumocystis jirovecii pneumonia
• Sepsis (including fatal outcome)
• Herpetic meningoencephalitis (including fatal outcome)
• Cytomegalovirus infection
• Cytomegalovirus reactivation
• Hepatitis B virus (including fatal outcome)
• Herpes simplex
• Infection reactivation
• Wound infection
• Gastroenteritis
• Myelodysplastic syndrome
• Secondary malignancies
• Myeloid leukaemia
• Febrile neutropenia
• Neutropenia
• Thrombocytopenia
• Lymphopenia
• Leukopenia
• Anaemia
• Prolonged pancytopenia
• Aplastic anaemia (including fatal outome)
• Pancytopenia
• Petechiae  
• Anaphylaxis
• Fever
• Influenza-like symptoms
• Allergic reaction

Sensory Disorders

• Visual field defect
• Blurred vision
• Diplopia
• Hemianopia
• Vision disorder
• Eye pain
• Decreased visual acuity
• Dry eyes
• Hearing impairment
• Tinnitus
• Otitis media
• Hyperacusis
• Earache
  - Ear discomfort
• Deafness
  - Deafness bilateral
  - Deafness neurosensory
  - Deafness unilateral  
• Vertigo
• Taste perversion
• Parosmia
• Sensory disturbance

Others

• Radiation injury
  - Radiation skin injury
• Aggravated condition
• Rigors
• Pain

• Valproic acid 
• Myelosuppressive agents 
• Carbamazepine
• Phenytoin
• Sulfamethoxazole/trimethoprim
• Food

• Full blood count with differential and platelets
• Hepatic function

None routine. Specific cases may require

• Pregnancy test

Temozolomide is a triazene, which undergoes rapid chemical conversion at physiologic pH to the active monomethyl triazenoimidazole carboxamide (MTIC). The cytotoxicity of MTIC is thought to be due primarily to alkylation at the O⁶ position of guanine with additional alkylation also occurring at the N⁷ position. Cytotoxic lesions that develop subsequently are thought to involve aberrant repair of the methyl adduct.

Capsule 5mg

• Accord Temozolomide (Accord)
• Temintas (Eurolab)
• Temodal (MSD) originator

Capsule 20mg

• Accord Temozolomide (Accord)
• Temintas (Eurolab)
• Temodal (MSD) originator

Capsule 100mg

• Accord Temozolomide (Accord)
• Temintas (Eurolab)
• Temodal (MSD) originator

Capsule 140mg

• Temodal (MSD) originator

Capsule 180mg

• Temodal (MSD) originator

Capsule 250mg

• Accord Temozolomide (Accord)
• Temintas (Eurolab)
• Temodal (MSD) originator