Tomudex diluted with water for injection to a concentration of 0.5 mg / ml and further diluted in 50-250 ml of 0.9% sodium chloride or 5% dextrose (glucose) immediately prior to intravenous infusion.
Other drugs should not be mixed with Tomudex in one package.
The dissolved drug should be stored at 2- 8 o C for up to 24 hours.
Infusion tomudeksa recommended to begin tamoxifen citrate immediately after the dilution of the drug.
Divorced tomudeksa solution must be completely used within 24 hours or destroyed.
There is no need to protect from light and diluted dilute the drug.
Do not store partially used vials or dissolved preparation for later use.
Side effect On the part of the digestive system: nausea, vomiting, diarrhea, anorexia, mucositis, stomatitis, ulceration of the mucous membrane of the mouth, dyspepsia, constipation, gastrointestinal bleeding (in the background of inflammation of the mucous membranes of the gastrointestinal tract thrombocytopenia), increased activity of “liver” transaminases , hyperbilirubinemia, and increased alkaline phosphatase. The most commonly nausea ). Typically, these events are mild to moderate harkter (1-2 degrees according to thetamoxifen citrate scale). Diarrhea, which can occur at any time tomudeksa therapy, observed in 36% of cases and is also usually wears a light or moderate (grade 1-2 on the scale). However, it may develop severe diarrhea, especially pronounced when combined with gematotoksichnosti (in particular with leukopenia).
Hematopoietic system: leukopenia, neutropenia, anemia, thrombocytopenia. Inhibition of bone marrow blood is usually seen in the first 2 weeks after administration of Tomudex. Perhaps the development of neutropenia and thrombocytopenia 4 severity on a scale of WHO, which may be severe and life-threatening, especially in combination with toxic effects on the gastrointestinal tract. Metabolic and Nutritional Disorders: weight loss, dehydration, peripheral edema. On the part of the musculoskeletal system : arthralgia. From the nervous system: increased muscle tone (usually in the form of spasms), headache. skin and skin appendages: rash, sometimes accompanied by itching, desquamation of the epidermis, alopecia, increased sweating. From the senses: taste change, conjunctivitis. other: asthenia, fever, flu-like symptoms, less often – abdominal pain, pain at other sites, accession secondary infections, superficial abscess and sepsis.
Expected symptoms: increased suppression of bone marrow hematopoiesis and severity of dyspeptic disorders.
Treatment. Antidote to raltitrexed with proven clinical efficacy is unknown. Given the preclinical data that indicate a decrease in the toxic effect tomudeksa when using leucovorin, as well as clinical experience with other antifolates, an overdose as soon as possible is recommended to start the administration of folinic acid 25 mg / m 2 intravenously every 6 hours until the symptoms permit.
In the case of occurrence of toxicity tamoxifen citrate should be applied and supportive symptomatic treatment.
Interaction with other drugs and other forms of interaction.
Leucovorin (folinic acid), folic acid and vitamin preparations containing them, reduce the effectiveness of Tomudex, and therefore, these drugs should not be used right before or during administration of Tomudex.
Safety Study application raltitreksida in patients receiving or warfarin did not reveal clinically significant interactions.
Treatment Tomudex should be conducted only under the supervision of a physician who is experienced in the use of anticancer drugs.
Patients receiving therapy Tomudex should be carefully monitored for early signs of possible toxic and unwanted effects.
When using Tomudex should pay special attention to the condition of patients with suppressed function bone marrow, poor general condition, or after radiation therapy.
Patients with tumor progression after prior treatment of advanced chemotherapy disease with inclusion of 5-FU may also be insensitive to the action of Tomudex.
Before each administration of the drug required to monitor patterns of peripheral blood (including blood count and platelets) , the activity of “liver” transaminases, bilirubin and creatinine in serum.
The drug can be administered only under the following parameters of blood: white blood cell count ≥ 4000/mkl, neutrophil count ≥ 2000/mkl, platelet count ≥ 100000/mkl.
Repeated administration of the drug can only be with the disappearance of all signs of toxicity (particularly gastrointestinal and hematologic).
if signs of gastrointestinal toxicity, it is necessary to control the picture of peripheral blood (including blood count and platelets), at least 1 time per week to detect hematologic toxicity.
in the case of 4 degree of gastrointestinal toxicity (diarrhea or mucositis) or in the case of a combination of grade 3 gastrointestinal toxicity with grade 4 hematologic toxicity treatment Tomudex should stop and immediately begin to standard supportive care, which includes intravenous fluids and therapeutic measures to support bone marrow hematopoiesis . Perhaps intravenous leucovorin (folinic acid) at a dose of 25 mg / m 2 every 6 hours until symptoms disappear.
Further use of Tomudex in such patients is not recommended.
Men and women of childbearing age during treatment with Tomudex and for at least 6 months after cessation of therapy should use reliable methods of contraception.
Tomudex belongs to the class of cytotoxic drugs and must be handled according to accepted rules for such substances.
in case of contact of the drug with its skin should be rinsed thoroughly with water immediately. In case of eye medication, they should be rinsed with clean water by opening the eyelids, for at least 10 minutes. Necessary tamoxifen citrate medical follow up.
Some side effects of Tomudex, such as malaise and fatigue, may adversely affect driving ability and the performance of potentially hazardous activities that require high concentration and speed of psychomotor reactions.