Hebervital®
Drug containing granulocyte colony stimulating factor (GCSF or Filgrastim), Hebervital® restores the number of leukocytes in the blood and corrects the neutropenia caused by cytotoxic chemotherapy. It improves the quality of life of cancer patients and reduces the incidence of infections.
Subcutaneous injection and intravenous infusion
0.30 mg / 1 mL 0.48 mg / 1.6 mL
- Kit for 1 bulb of 1 mL or 1.6 mL
- Kit for 10 bulbs of 1 mL or 1.6 mL
- Multiple kit for 10 kits < / li>
- Multiple kit for 10 kits for 10 bulbs of 1 mL or 1.6 mL
Each 1 mL or 1.6 mL bulb contains Filgrastim (granulocyte colony stimulating factor) 0.30 mg or 0.48 mg; polysorbate 80; sorbitol; sodium acetate or sodium acetate x 3H 2 O; acetic acid; water for injection.
Temperature between 2 and 8 ° C. Do not freeze or shake.
Hebervital® is indicated to reduce the duration of neutropenia and the incidence of febrile neutropenia in patients with neoplasms, except for chronic myeloid leukemia and myelodysplastic syndromes in patients receiving conventional cytotoxic chemotherapy.
It is also indicated to reduce the duration of neutropenia and its clinical sequelae in patients undergoing myelosuppressive treatment followed by bone marrow transplantation and who present an increased risk of prolonged severe neutropenia. The safety and efficacy of Hebervital® are similar in adults and children undergoing cytotoxic chemotherapy.
Hebervital® is also indicated for the autogenous mobilization of progenitor cells into the peripheral blood or to accelerate hematopoietic recovery by infusing these hemocytoblasts, after myelosuppressive or myelosuppressive chemotherapy.
Prolonged administration of Hebervital® is indicated to increase the neutrophil count and reduce the incidence of infections and their duration in patients, both in children and adults, with severe neutropenia (congenital, cyclic or idiopathic), neutrophil count less than or equal to 0.5 x 10 9 / L and a history of serious or recurrent infections.
Hebervital® is also indicated for the treatment of persistent neutropenias (neutrophil count less than or equal to 1 x 10 9 / L) in patients infected with HIV in an advanced stage, with in order to reduce the risk of bacterial infection, when other options aimed at reducing neutropenia are inadequate.
Patients with a history of allergy to the product or to any of its components.
It should not be used to increase the dose of cytotoxic chemotherapy beyond established limits.
It should not be administered in patients with severe congenital neutropenia (Kostmann syndrome) with abnormal cytogenetics.
Treatment must be in collaboration with a cancer center that has the necessary diagnostic facilities, as well as sufficient experience in hematology and G-CSF treatment.
G-CSF can stimulate the growth of myeloid and non-myeloid cells, so it is necessary to monitor the count of leukocytes, platelets, among others, taking the specific behavior in certain situations (such as leukocytosis).
Hebervital® can be stable for up to 36 months in refrigeration between 5 ± 3 ° C.
Diluted Hebervital® solutions should not be prepared for more than 24 hours prior to administration and should be stored refrigerated at 2-8 ° C. They should not be diluted in saline solutions; the product may precipitate.
The most common clinical side effect when Hebervital® is administered at recommended doses is musculoskeletal pain, which is usually mild or moderate and responds well to the usual analgesics. There are also reports of headache, fever, pain at the injection site, vomiting, diarrhea, thrombocytopenia.
Less frequent is mild or moderate dysuria, and the literature reports isolated cases of hypotension that did not require clinical treatment.
The literature reports with similar commercials, in addition, splenomegaly, diarrhea, alopecia, osteoporosis and rash, as well as: vasculitis, hepatomegaly, anemia, epistaxis, alterations in liver enzymes, uric acid and glucose levels.
- Conventional cytotoxic chemotherapy: The recommended dose of Hebervital ® is 0.5 MIU (5 μg) / kg in a single daily dose subcutaneously .
- Myelosuppressive treatment and bone marrow transplantation: The recommended starting dose is 1.0 MIU (10 μg) / kg / day as a short 30-minute intravenous infusion, infusion 24-hour continuous intravenous or 24-hour continuous subcutaneous infusion. Hebervital ® must be diluted in 20 mL of 5% glucose solution.
The first dose of Hebervital® should be made after 24 hours of cytotoxic chemotherapy and within 24 hours of bone marrow infusion. Once the theoretical low point in neutrophil count has been exceeded, the daily dose of Hebervital ® should be adjusted according to the response of the neutrophils as follows:
Neutrophil count | Hebervital dose adjustment ® |
& nbsp; & gt; 1.0 x 10 9 / L for 3 consecutive days | Decrease to 0.5 MIU / kg / day |
If it is still & gt; 1.0 x 10 9 / L for another 3 consecutive days | Suspend treatment |
If it drops to & lt; 1.0 x 10 9 / L during treatment | Repeat the scheme |
Daily Hebervital® treatment should continue until the predicted trough point for the neutrophil count has been exceeded and the neutrophil count has returned to normal. After conventional chemotherapy in solid tumors, the necessary duration of treatment should be a maximum of 14 days. In acute myelogenous leukemia (after induction treatment), the duration of therapy can reach more than 30 days, depending on the type, dose, and regimen of cytotoxic chemotherapy applied.
- Mobilization of blood stem cells in peripheral blood (in patients undergoing myelosuppressive and myelosuppressive chemotherapy followed by autologous stem cells, with or without bone marrow transplantation):
The recommended dose of Hebervital® to mobilize hemocytoblasts without prior treatment is 1.0 MIU (10 µg / kg / day), as a continuous 24-hour subcutaneous infusion or a daily subcutaneous injection for 5 to 7 consecutive days . For administration as an infusion, Hebervital ® must be diluted in 20 mL of 5% glucose solution. Often, one or two leukapheresis on days 5 and 6 are sufficient. In other circumstances, supplemental leukapheresis may be necessary. The Hebervital ® dose should be maintained until the last leukapheresis.
The recommended dose of Hebervital ® to mobilize hemocytoblasts after myelosuppressive chemotherapy is 0.5 MIU (5 µg / kg / day), administered in subcutaneous injections from the first day after chemotherapy, until the predicted time of maximal neutropenia has passed and the neutrophil count has reached normal values. Leukapheresis should be performed during the period when the neutrophil count is between 0.5 x 10 9 / L and 5.0 x 10 9 / L. For patients who have not received intensive chemotherapy, a leukapheresis is usually sufficient. In all other cases, additional leukapheresis is recommended.
- Autogenous mobilization of progenitor cells into the peripheral blood (PBPC) in healthy donors in view of allogeneic stem cell transplantation: The recommended Hebervital® dose for mobilization of PBPC in healthy donors is 1 .0 MIU (10 mg / kg / day) subcutaneously for 4 to 5 days. Leukapheresis should begin on day 5 through day 6 if necessary, in order to collect a quantity of 4 x 10 6 CD34 + cells of recipient body weight.
- < em> Severe chronic neutropenia: Daily administration (0.5 MIU (5 µg / kg / day) subcutaneously until stabilization of the neutrophil count above 1.5 x 10 9 / L. Subsequently, the minimum effective and necessary maintenance dose is determined. After 1-2 weeks of treatment, the initial dose can be reduced by half or doubled, according to the patient’s response and criteria from the physician.
- Congenital neutropenia: The recommended starting dose is 1.2 MIU (12 μg / kg / day), subcutaneously, as a single dose or in divided doses .
- Idiopathic or cyclic neutropenia: The recommended starting dose is 0.5 MIU (5 μg / kg / day) subcutaneously, in a single dose or in divided doses.
In most cases, the subcutaneous route of administration is preferred and recommended; however, the choice of the most appropriate route of administration (subcutaneous or intravenous) will depend on the clinical circumstances of each patient.
- Pediatric use in oncology:
Hebervital ® has been studied in children under 18 years of age. The efficacy of the treatment has been evident in this age group, with an adequate safety profile. Data from clinical studies in pediatric patients as well as pharmacovigilance reports indicate that the safety and efficacy of Hebervital ® are similar in both adults and children receiving cytotoxic chemotherapy.
The recommended doses for children are identical to those for adults after myelosuppressive cytotoxic chemotherapy.
- HIV-infected patients:
Correction of neutropenia: The recommended starting dose of Hebervital® is 0.1 MIU (1 mg / kg / day) administered daily subcutaneously. It can be stepped up to 0.4 MIU (4 mg / kg / day) until a normal and stable neutrophil count is obtained and maintained (greater than 2 x 10 9 /L). p>
- Maintaining a normal neutrophil count: Once the neutropenia has been corrected, the minimum effective dose to maintain the neutrophil count should be established.
Interactions and incompatibilities have not been described so far.
During pregnancy, the potential risks to the fetus and the anticipated therapeutic benefits should be considered. It is not known if Hebervital® passes into breast milk; its use is not recommended in nursing mothers.
In case of manifestations of bone or muscle pain related to the application of the product, caution should be observed when handling cars, machinery, tools or others that require great attention and physical strength.
There are no references of symptoms of overdose with this drug. The absolute neutrophil count (ANC) in patients should be monitored, and treatment with GCSF should be discontinued in case the ANC greater than 10,000 / mm3, since higher levels have not shown beneficial effects.