Oxaliplatin

Registered South African indications:

• Metastatic colorectal cancer
• Adjuvant treatment of colon cancer

Contraindications  

• Hypersensitivity to the active ingredient or any of its excipients
• Breastfeeding
• Severe renal impairment (CrCl <30ml/min)
• Myelosuppression prior to starting treatment, as evidenced by baseline neutrophils <2x10⁹/l and/or platelet count of <100x10⁹/l
• Peripheral sensitive neuropathy with functional impairment prior to first course
• Re-administration of oxaliplatin to patients previously experiencing anaphylactic manifestations to oxaliplatin infusion

Cautions 

• History of hypersensitivity to platinum compounds
• Pregnancy
• Males and females of reproductive potential
• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• Severe and persistent myelosuppression
• History or predisposition for QT prolongation
• Electrolyte disturbances
  - Hypokalemia
  - Hypocalcaemia
  - Hypomagnesaemia
• Intraperitoneal administration (off-label route of administration)
• May impair ability to drive and operate machinery

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

Used for the treatment of

• Metastatic colorectal cancer (additional agents required)
• Adjuvant treatment of colon cancer (additional agents required)
  - Stage III (Dukes C) colon cancer after complete resection of primary tumour

---

Used in combination with 5-fluorouracil and folinic acid

---

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Caution; positive evidence of risk in animal studies
• To date, there is no available information on safety of use in pregnant women
• In animal studies, reproductive toxicity was observed. Consequently, oxaliplatin is not recommended during pregnancy and in women of childbearing potential not using contraceptive measures
• The use of oxaliplatin should only be considered after suitably appraising the patient of the risk to the foetus and with the patient's consent
• Appropriate contraceptive measures must be taken during and after cessation of therapy for 4 months for women

Breastfeeding

• Contraindicated 
• Excretion in breast milk has not been studied. Breastfeeding is contraindicated during oxaliplatin therapy

Fertility

• Oxaliplatin may have an anti-fertility effect. Due to the potential genotoxic effects of oxaliplatin, appropriate contraceptive measures must be taken during and after cessation of therapy during 4 months for women and 6 months for men. Male patients should seek advice on conservation of sperm prior to treatment because oxaliplatin may have an anti-fertility effect which could be irreversible

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended
  Patients should be closely monitored for adverse reactions and the dose adjusted according to toxicity
• Severe: Contraindicated

Hepatic Impairment 

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Peripheral sensory neuropathy
• Sensory disturbance
• Headache
• Dizziness
• Motor neuritis
• Meningism
• Dysarthria
• Reversible posterior leukoencephalopathy syndrome
• Depression
• Insomnia
• Nervousness
• Fatigue
• Seizures
• Ischemic or haemorrhagic cerebrovascular disorder

Cardiovascular Disorders

• Haemorrhage
• Deep vein thrombosis
• Hypertension
• QT prolongation
• Ventricular arrhythmias including Torsade de Pointes (may be fatal)
• Acute coronary syndrome (combination with 5-FU and bevacizumab)
• Myocardial infarction (combination with 5-FU and bevacizumab)
• Coronary arteriospasm (combination with 5-FU and bevacizumab)
• Angina pectoris (combination with 5-FU and bevacizumab)

Respiratory Disorders

• Dyspnoea
• Cough
• Epistaxis
• Rhinitis
• Upper respiratory tract infection
• Hiccups
• Pulmonary embolism
• Interstitial lung disease
• Pulmonary fibrosis
• Laryngospasm
• Pneumonia and bronchopneumonia (including fatal outcomes)

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Stomatitis
• Mucositis
• Abdominal pain
• Constipation
• Dyspepsia
• Gastroesophageal reflux
• Gastrointestinal haemorrhage
• Rectal haemorrhage
• Ileus
• Intestinal obstruction
• Colitis including clostridium difficile diarrhoea
• Pancreatitis
• Intestinal ischemia (including fatal outcomes)
• Gastrointestinal ulcer
• Gastrointestinal perforation
• Oesophagitis

Hepatobiliary Disorders

• Increased hepatic enzymes
• Increased bilirubin
• Increased lactate dehydrogenase
• Increased creatinine
• Liver sinusoidal obstruction syndrome/veno-occlusive disease of the liver
• Peliosis hepatis
• Nodular regenerative hyperplasia
• Perisinusoidal fibrosis
• Portal hypertension

Genitourinary Disorders

• Haematuria
• Dysuria
• Abnormal micturition frequency
• Haemolytic uremic syndrome
• Acute tubular necrosis
• Acute interstitial nephritis
• Acute renal failure

Endocrine and Metabolic Disorders

• Anorexia
• Hyperglycaemia
• Hypokalaemia
• Hyponatraemia
• Dehydration
• Hypocalcaemia
• Metabolic acidosis
• Increased serum alkaline phosphatase
• Increased weight (adjuvant setting)
• Decreased weight (metastatic setting)

Musculoskeletal Disorders

• Back pain
• Arthralgia
• Bone pain
• Rhabdomyolysis (including fatal outcomes)

Skin and Subcutaneous Tissue Disorders

• Skin disorders
• Alopecia
• Skin exfoliation (Hand & Foot syndrome)
• Rash
• Erythematous rash
• Hyperhidrosis
• Nail disorder
• Injection site reaction
  - Local pain
  - Local redness
  - Local swelling
  - Local thrombosis
  - Extravasation
  - Necrosis
• Flushing
• Hypersensitivity vasculitis

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Neutropenia
• Thrombocytopenia
• Leukopenia
• Lymphopenia
• Febrile neutropenia
• Immunoallergic thrombocytopenia
• Haemolytic anaemia
• Infection
• Neutropenic sepsis (including fatal outcomes)
• Sepsis (including fatal outcomes)
• Allergy/allergic reaction
  - Skin rash
  - Urticaria
  - Conjunctivitis
  - Rhinitis
• Anaphylactic/anaphylactoid reactions
  - Bronchospasm
  - Angioedema
  - Hypotension
  - Sensation of chest pain
  - Anaphylactic shock
• Delayed hypersensitivity
• Fever
• Disseminated intravascular coagulation (including fatal outcomes)
• Autoimmune pancytopenia
• Pancytopenia
• Secondary leukaemia

Sensory Disorders

• Conjunctivitis
• Visual disturbance
• Transiently reduced visual acuity
• Visual field disturbances
• Optic neuritis
• Transient vision loss
• Ototoxicity
• Deafness
• Dysgeusia

Others

• Pain
• Fall

• Agents known to cause QT interval prolongation
• Agents known to be associated with rhabdomyolysis

• Hepatic function
• Full blood count with differential
• Electrolytes

Specific cases may require

• INR
• Prothrombin time
• Pregnancy test
• ECG monitoring

Oxaliplatin is an antineoplastic active substance belonging to a new class of platinum-based compounds in which the platinum atom is complexed with 1,2- diaminocyclo-hexane (“DACH”) and an oxalate group. Oxaliplatin is a single enantiomer, (SP-4-2)-[(1R,2R)-Cyclohexane-1,2-diamine-kN, kN'] [ethanedioato(2-)-kO¹, kO²] platinum. Oxaliplatin exhibits a wide spectrum of both in vitro cytotoxicity and in vivo antitumour activity in a variety of tumour model systems including human colorectal cancer models. Oxaliplatin also demonstrates in vitro and in vivo activity in various cisplatin-resistant models. A synergistic cytotoxic action has been observed in combination with 5-fluorouracil both in vitro and in vivo. Studies on the mechanism of action of oxaliplatin, although not completely elucidated, show that the aqua-derivatives resulting from the biotransformation of oxaliplatin, interact with DNA to form both inter and intra-strand cross-links, resulting in the disruption of DNA synthesis leading to cytotoxic and antitumour effects.

Injection (per 5ml) 50mg

• Eloplat (Sandoz)
• Oplaxin (Accord)
• Oxaliplatin Key 50 (Key Oncologics)
• Oxilico 50 (Eurolab)

Injection (per 10ml) 50mg

• Eloxatin (Sanofi) originator
• Exiplat (Ranbaxy)
• Oxaliplatin 50mg/10ml (Fresenius Kabi SA)
• Oxaliplatin pch (Pharmachemie)
• Oxaliwin 50mg/10ml RTU (Sanofi Aventis) originator

Injection (per vial) 50mg

• Accord oxaliplatin (Accord)
• Intas oxaliplatin (Eurolab)
• Oxaliplatin (Accord)

Injection (per 5ml) 100mg

• Eloplat (Sandoz)
• Oplaxin (Accord)
• Oxaliplatin Key 100 (Key Oncologics)
• Oxilico 100 (Eurolab)

Injection (per 20ml) 100mg

• Eloxatin (Sanofi) originator
• Exiplat (Ranbaxy)
• Oxaliplatin 100mg/20ml (Fresenius Kabi SA)
• Oxaliplatin pch (Pharmachemie)
• Oxaliwin 100mg/20ml RTU (Sanofi Aventis) originator

Injection (per vial) 100mg

• Accord oxaliplatin (Accord)
• Intas oxaliplatin (Eurolab)

• Oxaliplatin (Accord)