Composition, form of production and packaging
Capsules are hard gelatinous, the case is white, the lid is green; the content of the capsules is a powder of white or light yellow color.
Calcium folinate 15 mg
Excipients: microcrystalline cellulose, silicon dioxide, magnesium stearate, titanium dioxide, iron oxide, indicotin, gelatin.
20 pcs. - vials of polypropylene (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Antidote antagonists of folic acid. Calcium folinate is a 5-formyltetrahydrofolate of calcium. It is a restored form of folinic acid and a necessary coenzyme for the synthesis of nucleic acids in cytotoxic therapy.
Calcium folinate is often used to reduce toxicity and neutralize the action of folic acid antagonists, such as methotrexate. Calcium folinate and folate antagonists are carried by the same transport agents and compete for each other for transport to the cell, which causes an outflow of folate antagonists. It also protects cells from the effects of the latter by reducing the pool of folate. Calcium folinate serves as a source of H4 folate, so it can bypass the block of folate antagonists and provide a source for various coenzyme forms as folic acid.
Also calcium folinate is often used for biochemical modulation of fluorouracil in order to enhance its cytotoxic effect. Fluorouracil inhibits thymidylate synthetase, the key enzyme involved in the biosynthesis of pyrimidine. Calcium folinate enhances the inhibition of thymidine synthetase by increasing the intracellular folate pool, thus stabilizing the fluorouracil-thymidine synthetase complex and increasing its activity.
When administered inside a single dose of 20 mg of calcium folinate 98% is absorbed from the gastrointestinal tract. When taking 60 mg and 100 mg, bioavailability decreases from 62% to 42%, since the absorption of calcium folinate into the gastrointestinal tract is saturable.
Calcium folinate is a racemate, where the active enantiomer is the levorotatory form (L-5-formyltetrahydrofolate).
V d of folic acid is unknown.
The main metabolite of calcium folinata is 5-methyltetrahydrofolic acid, which is mainly formed in the mucosa of the intestine and liver.
All T 1/2 active metabolites with oral intake is 6.0 В± 1.9 h. If administered orally, 200 mg calcium folinate 20% is excreted with urine in the first 24 hours (5- and 10-formyltetrahydrofolates as inactive metabolites), 16% in the form of 5-methyltetrahydrofolic acid.
- Prevention of toxic effects of methotrexate, used in high doses;
- intoxication with folic acid antagonists (trimethoprim, pyrimethamine);
- megaloblastic anemia caused by a deficiency of folic acid (including against the background of malabsorption syndrome, malnutrition, pregnancy, sprue, in early childhood with congenital insufficiency of dihydrofolate reductase).
Capsules are taken orally. Doses of more than 50 mg are recommended for use in / in or / m, as the process of absorption of calcium folinate in the intestine is saturable.
Prevention of toxic effects of methotrexate
Calcium folinate prescription regimens depend on the regimens of therapy with medium and high doses of methotrexate, therefore it is advisable to consult the appropriate protocol for the treatment of methotrexate for the relevant information.
The following recommendations can serve as a guide for the determination of doses and schemes for the protective use of calcium folinate in adults, the elderly and children. The dose and duration of calcium folinate, first of all, depend on the doses and type of methotrexate therapy, the appearance of signs of toxicity and the specific features of methotrexate excretion.
Typically, the first dose of calcium folinate is 15 mg (6-12 mg / m 2 ), used no later than 12-24 hours after the onset of infusion of methotrexate. When high doses of methotrexate are used, doses of calcium folinate up to 120 mg can be administered by w / m or / or injection or infusion and then 15 mg orally every 6 hours for the next 48 h.
If lower doses of methotrexate are used, the administration of 15 mg calcium folinate for 48-72 hours after methotrexate administration may be sufficient.
Also an integral complement to the use of calcium folinate in the prevention of toxic effects of methotrexate are measures that promote the acceleration of excretion of methotrexate (ensuring the adequacy of urinary function and alkalinization of urine). The kidney function should be monitored daily by measuring the serum creatinine concentration.
It is recommended to measure the concentration of methotrexate in the blood serum 48 hours after the start of the infusion.
Prevention of the toxic effects of calcium methotrexate calcium folinate in patients with malabsorption syndrome or other gastrointestinal disorders (vomiting, diarrhea, etc.), when the enteral absorption is reduced, should be carried out by parenteral administration.
Intoxication with folic acid antagonists (trimethoprim, pyrimethamine)
After stopping the administration of trimethoprim, calcium folinate is used at a dose of 3-10 mg / day until the recovery of peripheral blood values.
In the case of high doses of pyrimethamine or prolonged treatment with low doses, calcium folinate should be used simultaneously at a dose of 5-50 mg / day, depending on the parameters of the peripheral blood.
With megaloblastic anemia caused by a deficiency of folic acid, calcium folinate is prescribed in a dose of up to 5 mg / day (maximum to 15 mg / day).
According to the WHO, the undesirable effects are classified according to their frequency of development as follows: very frequent (? 10%), frequent (? 1%, <10%), infrequent (? 0.1%, <1%), rare (? 0.01% , <0.1%, very rare (<0.01%, including single cases).
From the immune system: very rarely - allergic reactions, including anaphylactic shock and urticaria.
From the side of the central nervous system: rarely - insomnia, anxiety, depression when taking high doses, increasing the incidence of epileptic seizures.
From the digestive system: rarely - nausea, dyspepsia (when using high doses).
Other: infrequently, fever.
- megaloblastic anemia, caused by a deficiency of cyanocobalamin (vitamin B 12 );
- rare hereditary lactose intolerance, lactase deficiency or impaired glucose / galactose absorption (the preparation contains lactose);
- Children's age under 3 years (for this dosage form).
- hypersensitivity to calcium folinate or any other component of the drug.
With caution should be used in patients with epilepsy, chronic renal failure, alcoholism.
PREGNANCY AND LACTATION
Since no controlled studies have been conducted in pregnant women, the use of the drug in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.
It is not known whether the drug is excreted in breast milk, so if calcium folinate is needed during lactation, the question of stopping breastfeeding should be addressed.
APPLICATION FOR FUNCTIONS OF THE LIVER
The presence of previous or methotrexate-induced renal failure, which is associated with delayed excretion of methotrexate, may require the use of higher doses or a longer duration of therapy with the Calciumfolinate-Ebene drug.
APPLICATION FOR CHILDREN
The drug in the form of capsules is contraindicated in children under 3 years of age.
Treatment of methotrexate and the preparation of Calciumfonate-Ebwee should be performed by a qualified oncologist in the hospital, provided that the necessary controls are available.
The use of the Calciumfolinate-Ebwee preparation may mask the clinical picture of a pernicious or other type of anemia caused by a vitamin B deficiency.
Many cytotoxic drugs cause the development of macrocytosis (in particular, direct and indirect inhibitors of DNA synthesis - hydroxycarbamide, cytarabine, mercaptopurine, thioguanine). It is believed that such macrocytosis does not require treatment with folic acid.
In patients with epilepsy receiving treatment with phenobarbital, primidon, phenytoin, or succinimides, there is a risk of an increased incidence of epileptic seizures due to a decrease in plasma concentrations of antiepileptic drugs. In this case, it is recommended to conduct clinical monitoring, control of plasma concentrations of drugs and, if necessary, dose adjustment for antiepileptic drugs during the use of the Calciumfonolate-Ebweze and after the completion of the course of therapy.
Calciumfonolate-Ebwee does not protect against non-hematological toxic effects during methotrexate therapy (for example, from nephrotoxic action due to precipitation of methotrexate or its metabolites in the renal tubules). The presence of previous or methotrexate-induced renal failure, which is associated with delayed excretion of methotrexate, may require the use of higher doses or a longer duration of therapy with the Calciumfolinate-Ebene drug.
In the case of development of resistance to methotrexate due to the deterioration of the functioning of the membrane transport, resistance to calcium folinate also develops, since both drugs are transferred by the same transport system.
In case of an accidental overdose with a folic acid antagonist, such as methotrexate, emergency medical attention should be given, since an increase in the time interval between the use of methotrexate and the Calciumfoninate-Ebweave drug results in a decrease in the efficacy of the latter.
When clinical manifestations of toxicity or changes in laboratory parameters occur, the likelihood of the patient being administered other drugs that interact with methotrexate (for example, drugs that may affect the elimination of methotrexate or bind to blood plasma proteins) should always be considered.
Impact on the ability to drive vehicles and manage mechanisms
With the use of the drug Calciumfonilate-Ebwee, there was no effect on the ability to drive vehicles and to engage in other activities requiring concentration of attention and speed of psychomotor reactions.
The effect of taking significantly higher doses than recommended calcium doses of folate was not reported. However, high doses of calcium folinate can neutralize the chemotherapeutic effect of folic acid antagonists.
With the simultaneous use of folate calcium with folic acid antagonists (eg, co-trimoxazole, pyrimethamine), the efficacy of folic acid antagonists can be reduced or completely eliminated.
Calcium folinate can reduce the effectiveness of antiepileptic drugs (phenobarbital, primidon and phenytoin, succinimides) and increase the frequency of epileptic seizures (due to a decrease in the concentration of enzyme inducers of antiepileptic agents in the blood plasma because of the acceleration of metabolic processes in the liver, since folates are one of the co-factors ).
With combined use of calcium folinata and fluorouracil, the efficacy and toxicity of the latter increase.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light and out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.