Oxaliplatin infusion
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of oxaliplatin.
Drugs List
Therapeutic Indications
Uses
Metastatic colorectal cancer
Post-surgery adjuvant treatment of colon cancer
In combination with 5-fluorouracil and folinic acid in:
Adjuvant treatment of stage III (Duke's C) colon cancer after complete resection of primary tumour.
Treatment of metastatic colorectal cancer.
Dosage
Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer networks protocols and Trust chemotherapy protocols should be consulted.
Patients with Renal Impairment
Mild to moderate impairment - Creatinine clearance more than 30 ml per minute
Treatment may be initiated at the normally recommended dose.
One manufacturer recommends dosing patients with mild to moderate renal impairment at 85 mg/square metre.
Additional Dosage Information
Neurological symptoms
Patients who develop acute laryngopharyngeal dysaesthesia, during or within several hours after a 2-hour infusion: Next oxaliplatin infusion should be administered over 6 hours.
Other neurological symptoms the following dosage adjustments should be based on duration and severity of these symptoms.
Longer than 7 days and are troublesome: Subsequent dose should be reduced as follows:
Metastatic: From 85 mg/square metre to 65 mg/square metre.
Adjuvant: From 85 mg/square metre to 75 mg/square metre.
Paraesthesia without functional impairment persisting until the next cycle, the subsequent dose should be reduced:
Metastatic: From 85 mg/square metre to 65 mg/square metre.
Adjuvant: From 85 mg/square metre to 75 mg/square metre.
Paraesthesia with functional impairment persists until the next cycle, oxaliplatin should be discontinued.
If these symptoms improve following discontinuation of therapy, resumption of therapy may be considered.
For oxaliplatin and 5-fluorouracil combination (with/without folinic acid), the usual dosage changes apply for any 5-fluorouracil associated toxicities.
Haematological toxicity:
Neutrophils are less than 1.5 x 10 to the power of 9 per litre and/or platelets less than 50 x 10 to the power of 9 per litre, administration of the next course of therapy should be postponed until values return to acceptable levels.
When used together with 5-fluorouracil:
Grade 3 to 4 neutropenia (i.e. neutrophils less than 1 x 10 to the power of 9 per litre), febrile neutropenia (neutrophils less than 1 x 10 to the power of 9 per litre, temperature of greater than 38.3 degrees celsius or a sustained temperature of greater than 38 degrees celsius for more than 1 hour), or grade 3 to 4 thrombocytopenia (platelets less than 50 x 10 to the power of 9 per litre) occurs, reduce the dose of oxaliplatin in addition to adjustment of the dose of 5-fluorouracil to:
Metastatic: From 85 mg/square metre to 65 mg/square metre.
Adjuvant: From 85 mg/square metre to 75 mg/square metre.
Gastrointestinal symptoms
Grade 4 diarrhoea when oxaliplatin is given together with 5-fluorouracil, reduce the dose of oxaliplatin in addition to adjustment of the 5-fluorouracil dose to:
Metastatic: From 85 mg/square metre to 65 mg/square metre.
Adjuvant: From 85 mg/square metre to 75 mg/square metre.
Mucositis or stomatitis (with/without neutropenia): Next treatment should be delayed until recovery to grade 1 or less, and/or neutrophil count is more than or equal to 1.5 x 10 to the power of 9 per litre).
Administration
For intravenous infusion.
Oxaliplatin should always be administered before fluoropyrimidines e.g. 5-fluorouracil.
Contraindications
Children under 18 years
Neutrophil count below 2 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
Breastfeeding
Long QT syndrome
Peripheral neuropathy
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
History of treatment with anthracyclines
Electrolyte imbalance
History of torsade de pointes
Renal impairment
Administration of live vaccines is not recommended
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Concentrate must be diluted and used as an infusion
If extravasation occurs follow local policy & seek expert help immediately
Never rechallenge treatment after a hypersensitivity reaction
Reducing the infusion rate may minimise severity of infusion reactions
Treatment to be administered by or under supervision of specialist
Monitor full blood count and differential WBC before and during therapy
Perform ECG before and during treatment
Pre-treatment neurological examination recommended
Monitor closely patient with pre-existing renal impairment
Monitor serum electrolytes
Periodic neurological examination
Advise patient paraesthesias may persist up to 3 years after treatment ends
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to seek medical help if diarrhoea/emesis/neutropenia occur
Discontinue if a serious infection develops
Discontinue if intestinal ischaemia occurs
Discontinue if signs of gastro-intestinal ulceration occur
If mucositis/stomatitis occurs, delay next treatment until recovery
May reduce effectiveness of vaccinations during treatment
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Prophylactic antiemetic recommended before each dose
Risk of developing opportunistic infections
Discontinue at first signs of microangiopathic haemolytic anaemia
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if severe haematological toxicity develops until event resolves
Discontinue if signs of disseminated intravascular coagulation occur
Discontinue if unexplained respiratory symptoms occur
Discontinue immediately if rhabdomyolysis occurs
Reduce dose or discontinue if neurological symptoms develop and persist
May cause impaired fertility
Female: Contraception required during and for 4 months after treatment
Male: Contraception required during and for 6 months after treatment
Posterior Reversible Encephalopathy Syndrome (PRES)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with oxaliplatin. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed oxaliplatin treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Pregnancy and Lactation
Pregnancy
Oxaliplatin is contraindicated during pregnancy.
The manufacturer recommends that oxaliplatin is not used during pregnancy. There is currently limited information on the safety of use in human pregnancy. Reproductive toxicity was observed in animal studies and has been shown to be mutagenic and clastogenic in mammalian test systems.
Lactation
Oxaliplatin is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding is contraindicated during oxaliplatin treatment. It is not known whether oxaliplatin is excreted into breast milk. Due to the potential for serious adverse reactions in the infant, women should not breastfeed during therapy. Hale (2014) suggests breastfeeding is not advisable for many days (more than 20 to 30 days) and should probably be discontinued, unless milk platin could be measured.
Side Effects
Abdominal pain
Allergic reaction
Alopecia
Anaemia
Anorexia
Arthralgia
Asthenia
Back pain
Bone pain
Colitis
Conjunctivitis
Constipation
Cough
Deafness
Deep vein thrombosis (DVT)
Dehydration
Depression
Diarrhoea
Dizziness
Dysaesthesia
Dysarthria
Dysgeusia
Dyspepsia
Dysphagia
Dyspnoea
Dysuria
Epistaxis
Erythematous rash
Falling
Fatigue
Febrile neutropenia
Feeling of tightness in chest
Fever
Flushing
Gastro-intestinal haemorrhage
Gastroesophageal reflux
Haematuria
Haemolytic anaemia
Haemorrhage
Hand-foot syndrome
Headache
Hepatobiliary disorders
Hiccups
Hypercalcaemia
Hyperglycaemia
Hyperhidrosis
Hypertension
Hypokalaemia
Hyponatraemia
Ileus
Immunologically mediated thrombocytopenia
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increases in hepatic enzymes
Infections
Injection site reactions
Insomnia
Interstitial lung disease
Intestinal obstruction
Leucopenia
Loss of vision(transient)
Lymphopenia
Meningism
Metabolic acidosis
Micturition disorders
Mucositis
Muscle cramps
Nail disorders
Nausea
Nervousness
Neuritis
Neutropenia
Neutropenic sepsis
Oesophagitis
Optic neuritis
Ototoxicity
Pain
Pancreatitis
Paraesthesia
Peripheral neuropathy
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Pulmonary embolism
Pulmonary fibrosis
Rash
Rectal haemorrhage
Reduced visual acuity
Renal impairment
Rhinitis
Sensory disturbances
Sepsis
Serum bilirubin increased
Serum creatinine increased
Stomatitis
Thrombocytopenia
Upper respiratory tract infection
Visual disturbances
Vomiting
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 During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on 4th October 2019].
Martindale: The Complete Drug Reference, 39th edition (2017) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 16th Edition (2014) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Oxaliplatin 5mg/ml powder for solution for infusion. Accord UK Limited. Revised March 2019.
Summary of Product Characteristics: Oxaliplatin 5mg/ml concentrate for solution for infusion. Sun Pharmaceuticals UK Limited. Revised February 2019.
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