Recombinant human interferon alpha 2b.
Each vial of freeze dried powder contains: BIOFERON 3 million Recombinant human α2b interferon 3,000,000 IU.
BIOFERON 5 million Recombinant human α2b interferon 5,000,000 IU.
BIOFERON 10 million Recombinant human α2b interferon 10,000,000 IU.
Pharmacology: THERAPEUTICAL ACTION: The immune system is formed by a complex of different cells that cooperatively receive and issue several signals aimed at target cells, thus regulating the defense mechanisms of the organism. The molecules responsible for the mediation of this interaction are proteins, peptides and other substances that in virtue of their activity are called immunomodulators.
The biological immunomodulating signals are formed by a group of molecules with specific properties. Many of them have been chemically and biologically characterized while others still call for discovery.
To the moment, INTERFERON has been the most widely used of this kind of molecules in clinical medicine and investigation.
The first clinical trials using INTERFERON took place in 1970, using the alpha type produced in leukocytes obtained from normal donors, and research increased as production was optimized and larger amounts of this protein were available.
Recombinant DNA technology constituted a turning point in the production of rHulFNα2. The development of this technology and that of monoclonal antibodies gave rise to a significant advance in the therapeutical use of this molecule, since great amounts of a highly purified preparation could be obtained.
rHulFNα2b-Sidus is produced by recombinant DNA techniques expressed in E.coli. The protein obtained is of M.W. 19,000 Dalton with a specific activity of 2 x 108 IU/mg of protein. It has an antiviral, antiproliferative and immunomodulating therapeutical activity.
The use of rHulFNα2-Sidus can be indicated in: Virology: Clinical entities of viral etiology.
Human papillomavirus: Common warts, condylomata acuminatum located in penis, perineal region, anus, rectum, vulva, vagina, cervix, cervical, dysplastic entities associated to human papillomavirus, respiratory tract papillomatosis, epidermodysplasia
verruciformis, bladder papilloma.
Hepatitis Virus: Chronic hepatitis caused by hepatitis C virus and hepatitis B virus.
INTERFERON ALPHA induces inhibition of hepatitis B viral replication for long periods.
Inhibition takes place in hepatocites that contain virus in active replication.
Viral infections in patients with: Congenital immuno-suppression syndrome acquired immuno-depression syndrome (AIDS): Chemotherapy in neoplastic disease therapy; chemotherapy or corticoid therapy in patients with renal transplant or other grafts.
Oncology: Malignant melanoma; Kaposi's sarcoma associated to AIDS, renal cancer; carcinoid tumor; in situ carcinoma or the cervix associated AIDS.
Oncohaematology: Hairy cell leukemia, non-Hodgkin lymphoma, T-cell cutaneous lymphoma, multiple myeloma, chronic granulocyte leukemia.
According to medical indication.
Recommended dosage: Chronic Hepatitis B: Standard corporate-approved dosage regimen.
The recommended dosage is 30 to 35 million IU per week, administered subcutaneously or intramuscularly either as 5 million IU daily or 10 million IU three times a week for 16-24 weeks.
Pediatric (1 through 17 years of age): The recommended dosage is 3 million IU/m2 three times a week (every other day) for the first week of therapy followed by dose escalation to 6 million IU/m2 three times a week (maximum 10 million IU three times a week) administered subcutaneously for a total therapy duration 16 to 24 weeks.
Chronic Hepatitis C: The recommended dose is three million IU administered subcutaneously three times a week for up to 18-24 months.
Most patients who respond demonstrate improvement in ALT levels within 12-16 weeks. Some patients who fall to respond to three million IU may benefit from higher doses of up to 10 million IU three times a week.
Patients who relapse following BIOFERON therapy may be retreated with the same dosage regimen to which they previously responded.
Respiratory Tract Papillomatosis e.g. Laryngeal Papillomatosis: The recommended dosage of BIOFERON injection is 3 million IU/m2 administered subcutaneously three times a week (every other day), beginning after surgical (laser) removal of tumor tissue. The dosage may be adjusted according to patient's tolerance to medication. Response to treatment may require more than six months of therapy.
Condylomata Acuminatum: The lesion or lesions to be injected should be cleaned first with a sterile alcohol pad. The intralesional injection should be made into the center of the base of the lesion using a fine needle (30 gauge). Inject 0.1 mL of reconstituted solution containing 1.0 million IU BIOFERON injection into the lesion three times per week on alternate days, for three weeks. As many as five lesions can be treated at one time. The maximum total dose administered each week should not exceed 15 million IU.
Large lesions may be treated by multiple injections (up to a total of 5.0 million IU of BIOFERON per day) or by sequentially injecting different areas of the lesions.
Re-treatment-Improvement usually occurs four to eight weeks after initiation of the first treatment course. If results at this time are not satisfactory, a second course of treatment at the same dosage schedule may be instituted providing that clinical signs and symptoms or changes in laboratory parameters do not preclude re-treatment.
Treatment of additional lesions- Immediately following completion of the first three weeks of treatment, a second course may be instituted at the same dosage regimen to treat up to five additional lesions in patients with six to ten condylomata. Patients with greater than ten condylomata may receive treatment sequentially depending on how large a number of condylomata are present.
In clinical studies patients with condylomata also have been treated with BIOFERON administered intralesionally at a dose of 1.5 million IU per lesion followed by the topical application of 25% podophyllin. Treatment was given once a week for three weeks.
Malignant Melanoma: As adjuvant to surgery, BIOFERON injection is administered intravenously at a dose of 20 million IU/m2 five times weekly for four weeks, followed by 10 million IU/m2 administered subcutaneously three times weekly for 48 weeks.
In combination with chemotherapy for the treatment or patients with metastatic melanoma, BIOFERON injection is administered intravenously at a dose of 15 million IU/m2 five times weekly for three weeks, followed by 10 million IU/m2 administered subcutaneously three times weekly until disease progression or the physician feels it is no longer needed; patients have been treated for more than two years.
AIDS-Related Kaposi's Sarcoma: Treatment of patients with AIDS-related Kaposi's Sarcoma who have no history of opportunistic infection.
The optimal dosage is not yet known.
Efficacy has been demonstrated at a dose of 30 million IU/m2 three to five times a week, administered subcutaneously or intramuscularly. Lower doses (i.e., 10 to 12 million IU/m2/day) also have been used without apparent loss of efficacy.
Alternatively, BIOFERON injection may be administered at a dose of 50 million IU/m2 administered daily as a 30-minute intravenous infusion for 5 consecutive days followed by a minimum interval of 9 days until beginning the next 5 days treatment period.
When disease stabilization of treatment response occurs, therapy should continue until there is no further evidence of tumor or until discontinuation is required by evidence of a severe opportunistic infection or adverse effect.
Concomitant administration with Zidovudine (AZT)- In clinical studies, AIDS patients with Kaposi's Sarcoma have received BIOFERON concomitantly with AZT. In most patients, the following regimen has been well tolerated: BIOFERON at a dosage of 5 to 10 million IU/m2 daily; AZT 100 mg every four hours neutropenia is the major dose limiting toxicity. The dose of BIOFERON may be initiated at 3 to 5 million IU/m2 daily. After 2 to 4 weeks of therapy, depending upon patient tolerance, BIOFERON may be increased by 5 million IU/m2 daily to 10 million IU/m2 daily; AZT dosage may be increased to 200 mg every four hours, Dosage should be individualized based on patient response and tolerance to drug therapy.
Renal Cell Carcinoma: As monotherapy optimal dose and schedule have not been determined BIOFERON has been administered subcutaneously at dose ranging from 3 to 30 million either three times a week, five days per week, or daily. The highest response rates were achieved when BIOFERON was administered subcutaneously at dose of 3 to 10 million IU/m2 three times a week.
In combination of with other therapeutic agents, such as interleukin-2, optimal dose has not been determined. BIOFERON has not been administered subcutaneously at doses ranging from 3 to 20 million IU/m2 in combination with interleukin-2. In the trials reporting the highest overall response rates, BIOFERON was administered subcutaneously at dose of 6 million IU/m2 three times a week; dose was adjusted as needed during treatments.
Hairy Cell Leukemia: The recommended dosage of BIOFERON injection is 2 million IU/m2 administered subcutaneously or intramuscularly three times a week (every other day). The dosage may be adjusted according to patient's tolerance to the medication.
Non-splenectomized patients responded similarly to splenectomized patients, with similar reduction in transfusion requirements.
The normalization of one or more hematologic variables usually begins within two months of therapy. Improvement in all three hematologic variables (granulocyte count, plalelet count and hemoglobin level) may require six months or more. Prior to initiation of therapy, tests should be performed to quantitate peripheral blood hemoglobin, platelets, granulocytes and hairy cells, and bone marrow hairy cells. These parameters should be monitored periodically during treatment to determine whether response to treatment has occurred. If response occurs, treatment should be continued until no further improvement is observed and laboratory parameters have been stable for approximately three months. If no response to therapy occurs within 6 months, treatment should be discontinued. This regimen should be maintained unless the disease progresses rapidly or severe intolerance is manifested.
If treatment with BIOFERON has been interrupted, it should be noted that retreatment with BIOFERON has led to response in greater than 90% of patients.
Non-Hodgkin's Lymphoma: Adjuvant treatment of high tumor burden follicular lymphoma (Stage III or IV) in combination with appropriate chemotherapy, such as a CHOP-like regimen. BIOFERON injection also is indicated in the treatment of patients with low-grade Non-Hodgkin's Lymphoma.
Non-Hodgkin's Lymphoma- Adjunctively with chemotherapy, BIOFERON injection may be administered subcutaneously, at a dose of 5 million IU three times a week (every other day).
Cutaneous T-Cell Lymphoma (Mycosis Fungoides): In patients with plaque stage mycosis fungoides, BIOFERON injection has induced clinical regression when injected intralesionally at a dose of 1 million or 2 million IU per injection site three times a week for four consecutive weeks.
The lesion or lesions to be injected should be cleaned first with a sterile alcohol pad; the needle is directed at an angle almost parallel to the plane of the skin. Inject intralesionally into the superficial dermis beneath the patch or plaque using a fine needle (30 gauge) and a 1 mL syringe. Care should be taken not to go beneath the lesion too deeply and subcutaneous injections should be avoided. Repeat this procedure three times a week for four weeks for a total of 12 injections per lesion. In clinical trials, improvement in lesion sites was noted to continue several weeks after conclusion of intralesional therapy administered at a total dose of 2 million IU per visit.
Multiple Myeloma: As part of induction therapy, as maintenance therapy in patients who achieved objective remission on induction therapy, and in patients who have relapsed.
Multiple Myeloma-Induction therapy: Adjunctively to induction chemotherapy, BIOFERON may be administered subcutaneously at a dose of 3 to 5 million IU/m2 three times a week (every other day) throughout the duration of the induction phase.
Maintenance therapy: In patients who are in the plateau phase following induction chemotherapy, BIOFERON may be administered subcutaneously as monotherapy, at a dose of 3 to 5 million IU/m2 three times a week.
Therapy following relapse or refractory disease: In patients who have experienced relapse following chemotherapy or who have disease refractory to chemotherapy, BIOFERON may be administered as monotherapy at a dose of 3 to 5 million IU/m2 three times a week.
Route of Administration: Subcutaneous, intramuscular or intravenous injection.
Reconstitute the freeze dried powder in 1 mL of diluent. Vary the site of injection for repeated administration. Administer with the disposable material supplied. The use of glass syringe is not recommended since the polypeptide adheres to its surface, thus diminishing the final concentration of the preparation.
Antagonisms and Antidotisms: None.
Known hypersensitivity to INTERFERON.
Even though teratogenic studies have proved not to exert significant effects, do not administer to women during pregnancy or lactation.
It is recommended to monitor patients receiving INTERFERON for long periods and in high doses with the following laboratory analyses: White blood cell and platelet count, dosage of hepatic enzymes (TGO and TGP), evaluation of renal function (urea, creatinine).
Patients with history of cardiac abnormalities should be monitored by ECG during INTERFERON administration since arrhythmia may occur in some cases.
Since INTERFERON may affect the functions of the Central Nervous System, patients should be prevented to be cautious to drive vehicles and operate equipment till good tolerance to treatment is assessed.
During INTERFERON administration, an adequate hydration should be maintained since the feasibility of hypertension occurrence is related to depletion of liquids.
This drug is contraindicated for pregnant and lactating women.
Do not administer to women during pregnancy or lactation.
Site of Injection:
In some cases pain and erythema was observed in the site of injection, symptoms that are well tolerated.
The most frequent side effect is fever, which may be controlled with the use of paracetamol. This adverse effect is reversible and usually disappears during the first two weeks of treatment. Other frequent adverse effects that may occur are:a)Flu-like syndrome (headaches, hyperthermia, myalgia). This effect can also be controlled with paracetamol by administering 500 mg similar to the ones caused by a common flu (hyperthermia, shivering, headache, myalgia); b) Anorexia, asthenia, nausea or diarrhea may occur; c) Diminishment of number of circulating leukocytes and platelets. These parameters should be monitored with monthly laboratory count. It has been described in some cases and only with doses over 100 million daily units, side effects such as depression, confusion, somnolence, apathy and coma.
Extrapyramidal depression, cerebelous ataxia, cardiac arrhythmia, transaminase elevation and autoimmune diseases (autoimmune hemolytic anemia; thyroiditis, autoimmune thrombocytopenic purpura) have been seldom reported.
The use of INTERFERON is fully compatible with other antineoplastic and/or antiviral drugs. Administration of INTERFERON together with drugs that exert their effect on the Central Nervous System has seldom produced alterations in behavior.
L03AB05 - interferon alfa-2b ; Belongs to the class of interferons. Used as immunostimulants.
Inj (vial) 3 MIU x 1's. 5 MIU x 1's.