- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Ifosfamide for parenteral use
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 network protocols and Trust chemotherapy protocols should be consulted.
Patients with Renal Impairment
Decreased renal function may mean higher concentrations of ifosfamide in patient plasma. This may lead to toxicity and thus should be considered when determining dose.
Ifosfamide and its metabolites are dialyzable.
The Renal Drug Handbook suggests
Glomerular filtration rate (GFR) less than 60 and greater than 15 ml/minute
80% of normal dose
Glomerular filtration rate (GFR) less than 15 ml/minute
60% of normal dose
Patients with Hepatic Impairment
Hepatic impairment can mean decreased activation of ifosfamide. This may alter the effectiveness of ifosfamide treatment.
Hepatic impairment may increase the formation of a metabolite that is thought to contribute to CNS toxicity and nephrotoxicity. This should be considered when selecting the dose and interpreting response to the dose selected.
To be administered by intravenous injection or infusion.
Ifosfamide should only be used with the concurrent administration of mesna to protect against urothelial toxicity. Where intravenous injection of ifosfamide is used (rather than infusion) additional doses of mesna may be required. This is particularly the case in children, those with previous urothelial damage and those who are not adequately protected by standard mesna doses.
Leucocyte count below 4 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Renal impairment - serum creatinine above 120micromol/l
Urinary tract infection
Precautions and Warnings
Children under 18 years
History of platin treatment
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Consider diuretic if inadequate urinary output
Consider risk factors for CNS toxicity prior to initiating
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Prophylactic G-CSF should be considered
Treatment to be prescribed under the supervision of a specialist
Staff: Not to be handled by breastfeeding staff
Staff: Not to be handled by pregnant staff
Monitor haematological parameters before and during treatment
Urinalysis required pre and post treatment
Monitor for haematuria 4 hourly during treatment
Monitor for proteinuria 4 hourly during treatment
Advise patient to report signs or symptoms of cystitis
Concurrent mesna required to limit urothelial toxicity
May affect immune response to live vaccines
Prophylactic antiemetic recommended before each dose
Reactivation of latent chronic infections may occur
Secondary tumours may occur as long-term sequelae
Stop treatment if CNS toxicity suspected and provide supportive therapy
Discontinue if hypertensive encephalopathy occurs
Interrupt therapy if urinary tract infection occurs
Suspend treatment if leucocytes fall below 4,000/cubic mm
Suspend treatment if platelets fall below 100,000/cubic mm
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Male & female: May cause infertility
Female: Contraception required during and for 1 year after treatment
Male: Contraception required during and for 6 months after treatment
Advise increased fluid intake for 24-48 hours post treatment
Advise patient of need for high oral hygiene standards
Dose selection for elderly patients should be cautious due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease and/or other drug therapy.
Patients should maintain adequate hydration prior to and during treatment. Fluid intake of patients on intermittent regimens should be at least 2 litres in 24 hours.
Concurrent mesna is required to limit urothelial toxicity. Where ifosfamide is used as an intravenous bolus, increased doses of mesna are recommended in children, patients whose urothelium may be damaged from previous therapies and those who are not adequately protected by the standard dose of mesna.
The risk of myelosuppression is dose dependent; a single high dose carries a greater risk than fractionated administration. The risk of myelosuppression is also higher in patients with renal impairment. Administration of ifosfamide is associated with a reduction in the leukocyte count. The leukocyte nadir is usually seen during the second week after administration, after which, the leukocyte count rises again. Close haematological monitoring is advised; including white blood cell count, platelet count and haemoglobin levels. These should be obtained prior to each administration of ifosfamide and at regular intervals during therapy.
Ifosfamide may cause CNS toxicity and other neurotoxic effects. This may become evident within a few hours to a few days after the initial administration and usually resolves within 48 to 72 hours of ifosfamide discontinuation. In addition to dose dependant CNS toxicity, other supplementary risk factors may increase a patients possibility of CNS toxicity. These risk factors include electrolyte imbalances, presence of brain metastases, previous CNS disease, brain irradiation, cerebral sclerosis and peripheral vasculopathy. Also, a lower abdomen tumour, bulky abdomen disease, poor performance status, advanced age, obesity and female gender may affect an individuals potential to experience CNS toxicity.
The risk of developing cardiotoxic effects is dose dependent. It is increased in patients with prior or concomitant treatment with other cardiotoxic agents or radiation of the cardiac region and, possibly, renal impairment.
The risk of haemorrhagic cystitis is dose dependent; a single high dose carries a greater risk than fractionated administration.
Girls who have retained ovarian function after completing treatment are at increased risk of developing premature menopause.
Some degree of testicular atrophy may occur. Azoospermia may be reversible in some patients, though the reversibility may not occur for several years after cessation of therapy.
Pregnancy and Lactation
Ifosfamide is contraindicated in pregnancy.
There is limited data available on the use of ifosfamide during pregnancy. Foetal growth retardation and neonatal anaemia have been reported in infants of mothers who received ifosfamide-containing chemotherapy regimes. Congenital deviations in infants have been reported in cases where the mother received ifosfamide during the first trimester of pregnancy.
Based on animal studies, human case reports and ifosfamide's mechanism of action, it is advised not to use ifosfamide during pregnancy, particularly during the first trimester. The benefit for the mother will need to be assessed against the risk for the foetus. The pregnant patient should be counselled on the potential risk to the foetus.
Animal data generated with cyclophosphamide, another oxazaphosphorine cytotoxic agent, suggests that an increased risk of failed pregnancy and malformations may remain even after treatment with the agent has ceased as long as the oocytes/follicles exist that were in any maturation phase when exposed to the agent.
Ifosfamide has been shown to be teratogenic in three species of animal and also to be both mutagenic and carcinogenic. Due to this and the similarity with cyclophosphamide, a known human teratogen, ifosfamide should be considered to have a high potential for human teratogenicity and embryo/foetal toxicity (Briggs, 2015).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Ifosfamide is contraindicated in breastfeeding.
Ifosfamide is excreted in breast milk and may cause neutropenia, thrombocytopenia, low haemoglobin concentrations and diarrhoea in the nursing infant.
Hale (2014) suggests withholding breastfeeding for at least 72 hours.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Acute respiratory distress syndrome
Blood pressure changes
Capillary leak syndrome
Deep vein thrombosis (DVT)
Growth retardation (children)
Haemolytic uraemic syndrome
Hepatic veno-occlusive disease
Hyperpigmentation of skin
Impaired gonadal function
Inappropriate secretion of antidiuretic hormone
Interstitial lung disease
Local reaction at injection site
Mental status changes
Portal vein thrombosis
Radiation recall dermatitis
Renal structural changes
Risk of secondary tumours as late sequelae
Toxic epidermal necrolysis
Tumour lysis syndrome
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 ).
Last Full Review Date: November 2016
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 30 September 2016.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 30 September 2016.
Summary of Product Characteristics: Ifosfamide injection 1g. Baxter Healthcare Ltd. Revised February 2014.
Summary of Product Characteristics: Ifosfamide injection 2g. Baxter Healthcare Ltd. Revised February 2014.
Already a member? Log in
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.