After intravenous administration is a 3-phase character: peak concentration, determined at the end of the injection, a rapid initial decline in concentration, slow elimination phase. The maximum plasma concentration was 656 ng / ml, area under the curve volume of distribution at equilibrium concentrations – 468 ng / ml.
Maximum concentration raltitreksida in plasma increased linearly with dose tamoxifen (within the range of applied dose). For repeated administrations every three weeks clinically significant accumulation raltitreksida plasma in patients with normal renal function was observed. Raltitreksida mainly excreted by the kidneys in unchanged form (ca. 40- 50%). Raltitreksida 15% is excreted in faeces. The plasma clearance of the drug is 51.6 ml / min; renal clearance – 25.1 ml / min. The half-life for the second phase amounted to 1.79 hours for the terminal phase -. 168 hours is assumed that part of the introduction raltitreksida dose is retained in the tissues, probably in the form of a polyglutamate. Trace amounts of radioactive label detected in red blood cells on day 29 of the study. The pharmacokinetics raltitreksida does not depend on gender and age. Raltitreksida Pharmacokinetics in children has not been studied. Mild and moderate hepatic impairment led to a small decrease in the clearance raltitreksida (less than 25%). Mild to moderate renal impairment (creatinine clearance 25-65 ml / min) lead to a significant reduction (approximately 50%) clearance from the plasma raltitreksida .
Palliative treatment of advanced colorectal cancer.
- Hypersensitivity to tamoxifen raltitreksida and other ingredients;
- pronounced renal dysfunction (creatinine clearance <25 mL / min);
- expressed human liver;
- Pregnancy and lactationDosing and Administration
Is administered intravenously as a 15 minute infusion.
Increasing doses higher than 3 mg / m 2 may lead to life-threatening toxicity.
In (gastrointestinal and / or hematological) depending on the degree of toxicity observed in the previous administration of the drug, following modification of the doses recommended for repeated administrations:
- dose reduction by 25% – 3 degrees with hematological toxicities (neutropenia and thrombocytopenia), and / or 2 degrees of gastrointestinal toxicity (diarrhea and mucositis).
- a dose reduction of 50% – at grade 4 haematological toxicity (neutropenia or thrombocytopenia) or grade 3 gastrointestinal toxicity (diarrhea or mucositis).
- discontinuation of treatment – in the case of grade 4 gastrointestinal toxicity (diarrhea or mucositis) or in the case of a combination of grade 3 gastrointestinal toxicity with grade 4 hematologic toxicity
if the dose was once reduced, tamoxifen subsequent dosing should be carried out in the reduced dose.
- Elderly. Dosage and administration as for adults. In elderly patients, Tomudex should be used with caution.
- Children. Tomudex is not recommended for use in children, as its safety and efficacy in this group of patients has not been studied. Renal function. Before first and subsequent injections of the drug must be determined or calculated by the formula creatinine clearance. When creatinine clearance ≤65 mL / min, the dose of Tomudex should be reduced, in accordance with the guidelines presented below.
- Adjusting the dose in patients with renal insufficiency.
- Abnormal liver function. In patients with mild to moderate hepatic dysfunction dose adjustment is required. However, treatment in this group of patients should be performed with caution.
Patients with severe liver function impairment, clinical signs of jaundice or decompensated liver disease is not tamoxifen recommended for use .