Raltitrexed parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Injection containing raltitrexed.
Drugs List
Therapeutic Indications
Uses
Advanced colorectal cancer(5-FU regimes not tolerated)-palliative treatment
Dosage
The dose is calculated on the basis of the body surface area.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Adults
The recommended dose is 3 mg/square metre body surface area, as a single short intravenous infusion in 50 to 250 ml 0.9% sodium chloride injection or 5% dextrose injection over 15 minutes.
Repeat treatment every 3 weeks if toxicity does not occur.
Dose escalation above 3 mg/square metre body surface area is not recommended, since higher doses have been associated with an increased incidence of life-threatening or fatal toxicity.
Elderly
(See Dosage; Adult)
Patients with Renal Impairment
Creatinine clearance 55 to 65 ml/minute:
75% of dose every 4 weeks
Creatinine clearance 25 to 54 ml/minute:
50% of dose every 4 weeks
Additional Dosage Information
Dose modification in the presence of gastrointestinal and haematological toxicity
Before initiation of treatment and before each subsequent treatment a full blood count (including a differential count and platelets), liver transaminases, serum bilirubin and serum creatinine measurements should be performed.
The total white cell count should be greater than 4,000 per cubic millimetre, the neutrophil count greater than 2,000 per cubic millimetre and the platelet count greater than 100,000 per cubic millimetre prior to treatment.
Any signs of toxicity from previous doses, particularly diarrhoea or mucositis and/or neutropenia of thrombocytopenia, must have resolved before subsequent doses are given.
Monitor full blood counts weekly in patients with gastrointestinal toxicity to detect signs of haematological toxicity.
Once toxicity has been completely resolved (by withdrawing scheduled doses until toxic signs regress) the following dose reductions are recommended:
25% dosage reduction in patients with :
WHO grade 3 haematological toxicity (neutropenia or thrombocytopenia)
WHO grade 2 gastrointestinal toxicity (diarrhoea or mucositis)
50% reduction in patients with:
WHO grade 4 haematological toxicity (neutropenia or thrombocytopenia)
WHO grade 3 gastrointestinal toxicity (diarrhoea or mucositis)
Once a dose reduction has been made all subsequent doses should be reduced.
It is essential that the dose reduction regime is adhered to due to the life-threatening effects of the toxicity.
Discontinue treatment in patients with:
WHO grade 4 gastrointestinal toxicity (diarrhoea or mucositis)
WHO grade 3 gastrointestinal toxicity associated with WHO grade 4 haematological toxicity
Patients with such toxicity should be given standard supportive care including intravenous hydration and bone marrow support.
The administration of folinic acid should also be considered.
Re-introduction to raltitrexed therapy is not recommended.
Contraindications
Children under 18 years
Breastfeeding
Decompensated liver disease
Jaundice
Pregnancy
Renal impairment - creatinine clearance below 25 ml/minute
Severe hepatic impairment
Precautions and Warnings
Debilitation
Elderly
History of radiotherapy
Hepatic impairment
Myelosuppression
Renal impairment
Reduce dose and/or alter dose interval in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Do not mix with other drugs or substances
Staff: Not to be handled by pregnant staff
Before each treatment monitor full blood count, renal and hepatic function
Exclude pregnancy prior to initiation of treatment
Monitor adverse reactions, especially gastrointestinal toxicity
Monitor toxicity - discontinue or modify dose if necessary
Discontinue if WHO grade 3 GI/grade 4 haematological toxicity occurs
Discontinue in patients with WHO grade 4 gastrointestinal toxicity
Male & female: Contraception required during & for 6 months after treatment
Pregnancy and Lactation
Pregnancy
Raltitrexed is contraindicated in pregnancy.
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 ).
Lactation
Raltitrexed is contraindicated in breastfeeding.
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
Side Effects
Abdominal pain
Alopecia
Anaemia
Anorexia
Arthralgia
Asthenia
Cellulitis
Conjunctivitis
Constipation
Dehydration
Desquamation
Diarrhoea
Dyspepsia
Fever
Gastro-intestinal toxicity
Gastrointestinal bleeding
Haematological toxicity
Headache
Hyperbilirubinaemia
Hypertonia
Increase in alkaline phosphatase
Increase in serum ALT/AST
Infections
Influenza-like syndrome
Leucopenia
Malaise
Mouth ulcers
Mucositis
Nausea
Neutropenia
Pain - generalised
Peripheral oedema
Pruritus
Rash
Sepsis
Stomatitis
Sweating
Taste disturbances
Thrombocytopenia
Vomiting
Weight loss
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: January 2014
Reference Sources
Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [December 20, 2013]].
Summary of Product Characteristics: Tomudex. AstraZeneca. Revised June 2013.
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