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TOMUDEX is a brand name for Raltitrexed, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TOMUDEX (raltitrexed) is indicated in the treatment of advanced colorectal cancer. 1.1 Pediatrics Pediatrics (<18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use (see section
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations As with other cytotoxic drugs, the administration of TOMUDEX (raltitrexed) is associated with certain adverse reactions; these mainly include reversible effects on the gastrointestinal tract, haematopoietic system and liver enzymes.
Prior to the 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.
2 Recommended Dose and Dosage Adjustment). Pregnancy should be excluded before treatment with TOMUDEX is commenced (see 2 CONTRAINDICATIONS). 2 Recommended Dose and Dosage Adjustment The dose of TOMUDEX (raltitrexed) is calculated on the basis of body surface area.
9% sodium chloride or 5% dextrose (glucose) solution. It is recommended that the infusion be given over a 15 minute period. In the absence of toxicity, treatment may be repeated every 3 weeks. Dose escalation above 3 mg/m2 is not recommended, since higher doses have been associated with an increased incidence of life threatening or fatal toxicity.
In the event of toxicity the next scheduled dose should be withheld until signs of toxic effects regress. In particular, signs of gastrointestinal toxicity (diarrhoea or mucositis) and haematological toxicity (neutropenia or thrombocytopenia) should have resolved completely before subsequent treatment is allowed.
Patients who develop signs of gastrointestinal toxicity should have their full blood counts monitored at least weekly for signs of haematological toxicity. Treatment in patients with suspected drug-related rises in liver enzymes should be deferred until they show evidence of reversibility to at least WHO grade 2.
Based on the worst grade of gastrointestinal and haematological toxicity observed on the previous treatment and provided that such toxicity has resolved completely, the following dose reductions are recommended for subsequent treatment: * 25% dose reduction: in patients with WHO grade 3 haematological toxicity (neutropenia or thrombocytopenia) or WHO grade 2 gastrointestinal toxicity (diarrhoea or mucositis).
* 50% dose reduction: in patients with WHO grade 4 haematological toxicity (neutropenia or thrombocytopenia) or WHO grade 3 gastrointestinal toxicity (diarrhoea or mucositis). Once a dose reduction has been made, all subsequent doses should be given at the reduced dose level.
1 Adverse Reaction Overview As with other cytotoxic drugs, the administration of TOMUDEX (raltitrexed) is associated with certain adverse reactions; these mainly include reversible effects on the gastrointestinal tract, haematopoietic system and liver enzymes.
Gastrointestinal system The most frequent effects were nausea (58%), vomiting (37%), diarrhoea (38%) and anorexia (28%). Other less frequent effects were mucositis, stomatitis (including mouth ulceration), dyspepsia and constipation.
Gastrointestinal bleeding which may be associated with mucositis and/or thrombocytopenia has been reported. PrTomudex® (raltitrexed) – Product Monograph Page 10 of 27 Diarrhoea is usually mild or moderate (WHO grade 1 and 2) and can occur at any time following the administration of TOMUDEX.
However, severe diarrhoea (WHO grade 3 and 4) can occur, and may be associated with concurrent haematological suppression, especially leucopenia (neutropenia in particular). Subsequent treatment may need to be discontinued or the dose reduced depending on the grade of toxicity (see 4 DOSAGE AND ADMINISTRATION).
Nausea and vomiting are usually mild (WHO grade 1 and 2), occur usually for the first week following the administration of TOMUDEX, and are responsive to antiemetics. Haematopoietic system Leucopenia (neutropenia in particular), anemia and thrombocytopenia, alone and in combination, have been reported as possible adverse drug reactions in clinical trials (22%, 18% and 5% of patients, respectively).
They are usually mild to moderate (WHO grade 1 and 2) and occur in the first or second week after treatment and recovering by the third week. Severe (WHO grade 3 and 4) leucopenia (neutropenia in particular) and thrombocytopenia of WHO grade 4 can occur and may be life threatening or fatal, especially if associated with signs of gastrointestinal toxicity.
4 Geriatrics). 2 CONTRAINDICATIONS TOMUDEX (raltitrexed) is contraindicated in patients with hypersensitivity to the drug or any of its components (see section 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING). 2 Breast-feeding).
TOMUDEX is not recommended for use in children (<18 years of age), as safety and efficacy have not been established in this group of patients. TOMUDEX is contraindicated in patients with severe renal and/or hepatic impairment. 1 Dosing Considerations As with other cytotoxic drugs, the administration of TOMUDEX (raltitrexed) is associated with certain adverse reactions; these mainly include reversible effects on the gastrointestinal tract, haematopoietic system and liver enzymes.
Prior to the 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.
2 Recommended Dose and Dosage Adjustment). Pregnancy should be excluded before treatment with TOMUDEX is commenced (see 2 CONTRAINDICATIONS). 2 Recommended Dose and Dosage Adjustment The dose of TOMUDEX (raltitrexed) is calculated on the basis of body surface area.
9% sodium chloride or 5% dextrose (glucose) solution. It is recommended that the infusion be given over a 15 minute period. In the absence of toxicity, treatment may be repeated every 3 weeks. Dose escalation above 3 mg/m2 is not recommended, since higher doses have been associated with an increased incidence of life threatening or fatal toxicity.
In the event of toxicity the next scheduled dose should be withheld until signs of toxic effects regress. In particular, signs of gastrointestinal toxicity (diarrhoea or mucositis) and haematological toxicity (neutropenia or thrombocytopenia) should have resolved completely before subsequent treatment is allowed.
). 4 Geriatrics). 2 CONTRAINDICATIONS TOMUDEX (raltitrexed) is contraindicated in patients with hypersensitivity to the drug or any of its components (see section 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING). 2 Breast-feeding).
TOMUDEX is not recommended for use in children (<18 years of age), as safety and efficacy have not been established in this group of patients. TOMUDEX is contraindicated in patients with severe renal and/or hepatic impairment.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Treatment should be discontinued in the event of any WHO grade 4 gastrointestinal toxicity (diarrhoea or mucositis) or in the event of a WHO grade 3 gastrointestinal toxicity associated with WHO grade 4 haematological toxicity. v. hydration and bone marrow support to help neutrophil and platelet recovery thus reducing the likelihood of fatal sepsis or haemorrhage.
Based on data in animals where delayed administration of leucovorin after TOMUDEX (raltitrexed) produced earlier recovery from weight loss and some improvement to intestinal damage and recovery of neutrophil and platelet numbers, consideration should be given to the administration of leucovorin (folinic acid).
v. every 6 hours until the resolution of symptoms. Further use of TOMUDEX in such patients is not recommended. It is essential that the dose reduction scheme be adhered to since the potential for life threatening and fatal toxicity increases if the dose is not reduced or treatment not stopped as appropriate.
Geriatric Patients:
Dosage and administration as for adults. 4 Geriatrics).
PrTomudex® (raltitrexed) – Product Monograph Page 6 of 27 Renal Impairment:
For patients with abnormal serum creatinine, before the first or any subsequent treatment, a creatinine clearance should be performed or calculated. For patients with a normal serum creatinine when the serum creatinine may not correlate well with the creatinine clearance due to factors such as age or weight loss, the same procedure should be followed.
0 mg/m2 Dosing interval > 65 mL/min Full dose 3-weekly 55 to 65 mL/min 75% 4-weekly 25 to 54 mL/min % equivalent to mL/min* 4-weekly <25 mL/min No therapy Not applicable *For example, if the creatinine clearance = 30 mL/min, 30% of the full dose should be given.
Patients with renal impairment may have an increased propensity for side-effects and should be monitored appropriately.
Hepatic Impairment:
No dosage adjustment is necessary for patients with mild (WHO grade 2) to moderate (WHO grade 3) hepatic impairment. However, given that a proportion of the drug is excreted via the faecal route (see 10 CLINICAL PHARMACOLOGY) and that these patients usually form a poor prognosis group, patients with mild (WHO grade 2) to moderate (WHO grade 3) hepatic impairment need to be treated with caution.
Treatment in patients with suspected drug -related rises in liver enzymes should be deferred until they show evidence of reversibility to at least WHO grade 2. TOMUDEX has not been studied in patients with severe hepatic impairment, clinical jaundice or decompensated liver disease and its use in such patients is not recommended.
Health Canada has not authorized an indication for pediatric use. 3 Reconstitution Parenteral Products: Each vial, […]
Hepatic Reversible increases in AST and ALT have been commonly reported as adverse drug reactions in clinical trials (16% and 14% of patients, respectively). Such changes have usually been asymptomatic and self limiting when not associated with progression of the underlying malignancy.
Other less frequent effects are weight loss, dehydration, peripheral edema, hyperbilirubinaemia and increases in alkaline phosphatase. Cardiovascular system A number of cardiac rhythm or cardiac function abnormalities have been reported in clinical trials in advanced colorectal cancer.
These ranged from sinus tachycardia and supraventricular tachycardia to atrial fibrillation and congestive heart failure. 4% for patients on the comparator treatment. A causal relationship could not be established since many of the abnormalities were concurrent with the underlying conditions such as sepsis and dehydration and more than one third of the patients reported cardiovascular abnormalities prior to treatment.
Musculoskeletal and Nervous System Arthralgia and hypertonia (usually muscular cramps) have each been reported as possible adverse drug reactions in less than 2% of patients who received TOMUDEX in clinical trials. Skin, Appendages and Special Senses Rash was commonly reported in clinical trials (14% of patients), sometimes associated with pruritus.
Other less frequent effects were desquamation, alopecia, sweating, taste perversion and conjunctivitis. Whole Body The most frequent effects in clinical trials were asthenia (49% of patients) and fever (22% of patients), which were usually mild to moderate following the first week of administration of TOMUDEX, and reversible.
Severe asthenia can occur and may be associated with malaise and a flu like syndrome. Other less frequent effects were abdominal pain, pain, headache, cellulitis and sepsis. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.
The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
The following effects were reported as possible adverse drug reactions occurring with an incidence of 2% or more in patients with colorectal cancer treated with TOMUDEX in clinical trials. Table 5 Drug-related adverse events reported for at least 2% of patients treated with TOMUDEX 3 mg/m2 in core colorectal cancer trials.
1% 50 […]
Patients who develop signs of gastrointestinal toxicity should have their full blood counts monitored at least weekly for signs of haematological toxicity. Treatment in patients with suspected drug-related rises in liver enzymes should be deferred until they show evidence of reversibility to at least WHO grade 2.
Based on the worst grade of gastrointestinal and haematological toxicity observed on the previous treatment and provided that such toxicity has resolved completely, the following dose reductions are recommended for subsequent treatment: * 25% dose reduction: in patients with WHO grade 3 haematological toxicity (neutropenia or thrombocytopenia) or WHO grade 2 gastrointestinal toxicity (diarrhoea or mucositis).
* 50% dose reduction: in patients with WHO grade 4 haematological toxicity (neutropenia or thrombocytopenia) or WHO grade 3 gastrointestinal toxicity (diarrhoea or mucositis). Once a dose reduction has been made, all subsequent doses should be given at the reduced dose level.
Treatment should be discontinued in the event of any WHO grade 4 gastrointestinal toxicity (diarrhoea or mucositis) or in the event of a WHO grade 3 gastrointestinal toxicity associated with WHO grade 4 haematological toxicity. v. hydration and bone marrow support to help neutrophil and platelet recovery thus reducing the likelihood of fatal sepsis or haemorrhage.
Based on data in animals where delayed administration of leucovorin after TOMUDEX (raltitrexed) produced earlier recovery from weight loss and some improvement to intestinal damage and recovery of neutrophil and platelet numbers, consideration should be given to the administration of leucovorin (folinic acid).
v. every 6 hours until the resolution of symptoms. Further use of TOMUDEX in such patients is not recommended. It is essential that the dose reduction scheme be adhered to since the potential for life threatening and fatal toxicity increases if the dose is not reduced or treatment not stopped as appropriate.
Geriatric Patients:
Dosage and administration as for adults. 4 Geriatrics).
PrTomudex® (raltitrexed) – Product Monograph Page 6 of 27 Renal Impairment:
For patients with abnormal serum creatinine, before the first or any subsequent treatment, a creatinine clearance should be performed or calculated. For patients with a normal serum creatinine when the serum creatinine may not correlate well with the creatinine clearance due to factors such as age or weight loss, the same procedure should be followed.
0 mg/m2 Dosing interval > 65 mL/min Full dose 3-weekly 55 to 65 mL/min 75% 4-weekly 25 to 54 mL/min % equivalent to mL/min* 4-weekly <25 mL/min No therapy Not applicable *For example, if the creatinine clearance = 30 mL/min, 30% of the full dose should be given.
Patients with renal impairment may have an increased propensity for side-effects and should be monitored appropriately.
Hepatic Impairment:
No dosage adjustment is necessary for patients with mild (WHO grade 2) to moderate (WHO grade 3) hepatic impairment. However, given that a proportion of the […]