Docetaxel

Registered South African indications:

• Breast cancer
• Non-small cell lung cancer
• Ovarian cancer
• Prostate cancer

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Baseline neutrophil count of <1500 cells/mm³
• Contraindications for other medicinal products also apply when combined with docetaxel

Cautions

• Prior history of hypersensitivity reactions to paclitaxel
• Pregnancy
• Breastfeeding
• Men of childbearing potential
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Patients with neutropenia at risk of developing gastrointestinal complications
• Severe fluid retention
  - Pleural effusion
  - Pericardial effusion
  - Ascites
• Concomitant radiation therapy
• Pre-existing cardiac dysfunction when used in combination with trastuzumab
• Alcoholism
• Epilepsy
• May impair ability to drive and operate machinery

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

Used for the treatment of

• Breast cancer
  - Adjuvant treatment of operable node-positive breast cancer in combination with doxorubicin and cyclophosphamide
  - Adjuvant treatment of operable node-negative breast cancer in combination with doxorubicin and cyclophosphamide. Adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer
  - In combination with doxorubicin for locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy
  - Monotherapy for locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent
  - In combination with trastuzumab for metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease
  - In combination with capecitabine for locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline
• Non-small cell lung cancer
  - Locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy
  - In combination with cisplatin for unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not previously received chemotherapy
• Ovarian cancer
  - After failure of first-line or subsequent chemotherapy for metastatic carcinoma of the ovary
• Prostate cancer 
  - In combination with prednisone or prednisolone for metastatic castration-resistant prostate cancer
  - In combination with androgen-deprivation therapy, with or without prednisone or prednisolone, for metastatic hormone-sensitive prostate cancer
• Gastric adenocarcinoma
  - In combination with cisplatin and 5-fluorouracil for metastatic adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease
• Head and neck cancer 
  - In combination with cisplatin and 5-fluorouracil for induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck

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Consult specialist for dosages and regimens

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats
• As with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated
• Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur. An effective method of contraception should be used during treatment

Breastfeeding

• Caution; not recommended
• Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk
• Consequently, because of the potential for adverse reactions in nursing infants, breastfeeding must be discontinued for the duration of docetaxel therapy

Fertility

• In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility
• Therefore, men being treated with docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Caution; no information available
  Certain formulations may contain macrogol 300 which may increase the risk of nephrotoxicity in patients with renal impairment

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
  Dose adjustment is recommended for elevations of transaminase (ALT and/or AST) >1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN
  For those patients with serum bilirubin >ULN and/or ALT and AST >3.5 times the ULN associated with alkaline phosphatase >6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated
• Severe: Contraindicated
  No data is available for severe hepatic impairment

Elderly

• Caution; no dose adjustment recommended
  - In combination with capecitabine, a starting dose reduction of capecitabine to 75% is recommended for patients ≥60 years
  - There is limited data available in patients >70 years on docetaxel use in combination with doxorubicin and cyclophosphamide
  - Incidence of adverse reactions may be more frequent in patients ≥65 years than in younger patients

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Peripheral sensory neuropathy
• Peripheral motor neuropathy
• Asthenia
• Peripheral neurotoxicity
  - Paraesthesia
  - Dysethesia
  - Pain including burning
• Insomnia
• Paraesthesia
• Hypoaesthesia
• Lethargy
• Dizziness
• Syncope
• Neurotoxicity
• Somnolence

Cardiovascular Disorders

• Arrhythmia
• Cardiac failure
• Hypotension
• Hypertension
• Haemorrhage
• Non-cardiac chest pain
• Lymphoedema
• Decreased left ventricular function
• Hot flush
• Myocardial ischaemia
• Venous disorder

Respiratory Disorders

• Dyspnoea
• Epistaxis
• Pharyngolaryngeal pain
• Nasopharyngitis
• Cough
• Rhinorrhoea
• Pharyngitis
• Upper respiratory tract infection

Gastrointestinal Disorders

• Stomatitis
• Diarrhoea
• Nausea and vomiting
• Constipation
• Abdominal pain
• Gastrointestinal haemorrhage
• Oesophagitis
• Dyspepsia
• Flatulence
• Oral candidiasis
• Dysphagia
• Odynophagia
• Dry mouth

Hepatobiliary Disorders

• Increased blood bilirubin
• Increased aspartate aminotransferase
• Increased alanine transaminase

Genitourinary Disorders

• Amenorrhoea

Endocrine and Metabolic Disorders

• Anorexia
• Increased blood alkaline phosphatase
• Increased weight
• Decreased weight
• Dehydration
• Diabetes
• Hypocalcaemia
• Hypophosphataemia
• Hypokalaemia
• Decreased appetite

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Pain in extremity
• Bone pain
• Back pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Skin reaction
• Eruptions
• Desquamation
• Hand-foot syndrome
• Nail disorders
  - Hypopigmentation
  - Hyperpigmentation
  - Pain
  - Onycholysis
• Infusion site reaction
  - Hyperpigmentation
  - Inflammation
  - Redness
  - Dryness of skin
  - Phlebitis
  - Extravasation
  - Swelling of the vein
• Mucosal inflammation
• Dermatitis
• Erythematous rash
• Exfoliative rash

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Anaemia
• Febrile neutropenia
• Thrombocytopenia
• Hypersensitivity  
  - Flushing
  - Rash
  - Pruritis
  - Chest tightness
  - Back pain
  - Dyspnoea
  - Fever
  - Chills
  - Hypotension
  - Bronchospasm
  - Generalised rash/erythema
• Infections  including sepsis and pneumonia (including fatal outcomes)
• Infection associated with Grade 4 neutropenia
• Bleeding episodes associated with Grade 3/4 thrombocytopenia
• Leucopenia (monotherapy in breast cancer)
• Neutropenic sepsis
• Fever
• Influenza-like illness
• Acute leukaemia
• Myelodysplastic syndrome

Sensory Disorders

• Dysgeusia
• Increased lacrimation
• Conjunctivitis
• Blurred vision
• Impaired hearing
• Parosmia

Others

• Fluid retention
  - Peripheral oedema
  - Pleural effusion
  - Pericardial effusion
  - Ascites
  - Weight gain
• Pain

• Strong CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Clarithromycin
• Indinavir
• Nefazodone
• Nelfinavir
• Ritonavir
• Saquinavir
• Telithromycin
• Voriconazole
• CYP450-3A inducers
• CYP450-3A inhibitors
• Agents metabolized by CYP450-3A
• Ciclosporin
• Erythromycin

• Hepatic function
• Full blood count

None routine. Specific cases may require

• Renal function
• Cardiac function
• Respiratory function
• Ophthalmic examination
• Pregnancy test

Docetaxel is an antineoplastic agent that acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of docetaxel to microtubules does not alter the number of protofilaments. Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for vital mitotic and interphase cellular functions.

Injection (per ml) 10mg

• Key Docetaxel 20mg and Diluent solution (Key Oncologics)
• Key Docetaxel 20mg and Diluent solution (Key Oncologics)

Injection (per vial) 20mg

• Axtere (Accord)
• Cipla docetaxel (Cipla)
• Docetere (Zentiva)
• Docefrez (Ranbaxy)
• Eriox (Eurolab)
• Eurotax 20mg (Eurolab)
• Taxocan 20 (Zydus Healthcare SA)

• Taxotere (Sanofi) originator

Injection (per ml) 20mg

• Docetere RTU (Sanofi Aventis South Africa)
• Docetaxel 20mg/ml Fresenius (Fresenius Kabi)
• Docetaxel 20 Teva (Teva Pharmaceuticals)
• Docetaxel Accord (Accord)
• Docetaxel Adco (Adcock Ingram Critical Care)
• Prosaglic 20 (Sandoz SA)

Injection (per vial) 80mg

• Axtere (Accord)
• Cipla docetaxel (Cipla)
• Docetere (Zentiva)
• Docefrez (Ranbaxy)
• Eriox (Eurolab)
• Eurotax 20mg (Eurolab)
• Taxocan 80 (Zydus Healthcare SA)
• Taxotere (Sanofi) originator

Injection (per 4ml) 80mg

• Docetere RTU (Sanofi Aventis South Africa)
• Docetaxel 80mg/4ml Fresenius (Fresenius Kabi)
• Docetaxel 80 Teva (Teva Pharmaceuticals)
• Docetaxel Accord (Accord)
• Docetaxel Adco (Adcock Ingram Critical Care)
• Prosaglic 80 (Sandoz SA)

Injection (per 8ml) 160mg

• Docetaxel Accord (Accord)