Raltitrexed


Concise Prescribing Info
Indications/Uses
Listed in Dosage
Dosage/Direction for Use
Adult : IV Initial: 3 mg/m2 given by IV infusion over 15 min. Repeat every 3 wk in the absence of toxicity. In the event of toxicity, withhold treatment and reduce subsequent doses.
Dosage Details
Intravenous
Palliative treatment of advanced colorectal cancer
Adult: 3 mg/m2 given by IV infusion over 15 min; doses above 3 mg/m2 is not recommended. Repeat every 3 wk in the absence of toxicity. In the event of GI toxicity (diarrhoea, mucositis) and haematological toxicity (neutropenia, thrombocytopenia), withhold treatment until such toxic effects have completely resolved. Subsequent doses should be reduced: WHO grade 3 haematologic toxicity or WHO grade 2 GI toxicity: 25% dose reduction; WHO grade 4 haematologic toxicity or WHO grade 3 GI toxicity: 50% dose reduction; WHO grade 3-4 GI toxicity associated with WHO grade 4 haematologic toxicity: Discontinue treatment.
Renal Impairment
CrClDosage
>65 mL/min3 mg/m2 every 3 wk
<25 mL/minDo not administer.
25-54 mL/min1.5 mg/m2 every 4 wk
55-65 mL/min2.25 mg/m2 every 4 wk
Reconstitution
Reconstitute each vial (2mg) with 4 mL of sterile water for inj to a concentration of 0.5 mg/mL using aseptic technique. Further dilute the appropriate dose of reconstituted solution with 50-250 mL of either 0.9% sodium chloride inj or 5% dextrose inj for admin via IV infusion over 15 min. Reconstituted and diluted solution do not need to be protected from light; it should be used as soon as possible. Use precaution for handling and disposal of cytotoxic agents.
Incompatibility
Compatible with 5% dextrose, 0.9% sodium chloride inj. Do not mix with other medications.
Contraindications
Severe renal impairment, pregnancy, and breastfeeding.
Special Precautions
Caution in patients with depressed bone morrow function, poor general condition, history of GI diseases or prior radiotherapy. Treatment may cause haematological and GI toxicity. Monitor FBC, liver transaminases, serum bilirubin and serum creatinine prior to initiation of therapy and before each subsequent treatment dose. Patients who did not respond to 5-fluorouracil based regimen may also resistant to Raltitrexed. May cause malaise or asthenia; caution when operating machinery or driving vehicle. Caution in elderly; renal impairment; mild to moderate hepatic impairment and avoid use in severe hepatic impairment. Safety and efficacy have not been established in paediatric patients. Avoid pregnancy during therapy and for at least 6 mth after discontinuance of treatment if either party is receiving Raltitrexed. Raltitrexed is cytotoxic; standard precaution for handling and disposal of cytotoxic agents should be used.
Adverse Reactions
Headache, nausea, vomiting, diarrhoea, abdominal pain, constipation, dehydration, dyspepsia, fever, rash, pruritus, pain, taste perversion, anorexia, weight loss, asthenia, malaise, arthralgia, infections, alopecia, mucositis, stomatitis, conjunctivitis, cellulitis, sepsis, peripheral oedema, anaemia, leucopenia, thrombocytopenia, hypertonia, hyperbilirubinaemia, increased AST and ALT, increased alkaline phosphatase, and increased serum creatinine.
Overdosage
Symptoms of overdose may be expected to be an exaggerated form of the adverse drug reactions. Clinically proven antidote is not available. In the event of overdose, may consider admin of folinic acid as suggested by preclinical data. IV folinic acid may be given at 25 mg/m2 6 hrly to counteract overdose toxicity. Monitor for signs of haematological and GI toxicity and provide symptomatic and supportive therapy.
Drug Interactions
Folic acid, folinic acid, methylfolate, and vitamin preparations containing these agents may interfere with the therapeutic action of Raltitrexed. Avoid use of these agents immediately before or during Raltitrexed therapy.
Action
Description: Raltitrexed is an antimetabolite used in treatment of colorectal cancer. It is a folate analogue which causes inhibition of DNA synthesis and cell death by acting as a direct and specific thymidylate synthase (TS) potent inhibitor.
Pharmacokinetics:
Distribution: Protein binding: About 93%. Vd at steady state: About 548 L.
Metabolism: Mainly by active transport into cells via reduced folate carriers to undergo extensive polyglutamation. The poylglutamate forms are retained in the cells and are more potent TS inhibitors. Minimal or no systemic metabolism.
Excretion: Excreted in urine (40-50% as unchanged drug); faeces (15%). Triphasic pharmacokinetics: β phase elimination half-life: About 1.79 hr; terminal half-life: Up to 198 hr. Plasma clearance is slightly reduced in mild to moderate hepatic impairment; significantly reduced (approx 50%) in mild to moderate renal impairment (CrCl 25-65 mL/min).
Storage
Unopened vial: Store at below 25°C, protect from light. Reconstituted vial: Refrigerate at 2-8°C; stable up to 24 hr.
Disclaimer: This information is independently developed by MIMS based on Raltitrexed from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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