Heberon Alpha R Immunomodulator

HEBERON ALPHA R

Human Recombinant Interferon Alfa – 2b

– Solution for injection (3, 5, 6 OR 10 M)

Human Recombinant Interferon Alfa – 2b

The solution contains 3, 5, 6, or 10 x 106 IU of human recombinant IFN alfa-2b, which is contained in hermetically sealed vials of

Application mode:

Intramuscular, subcutaneous, intravenous, intraperitoneal, intrathecal and intralecular

Composition:

Active ingredient: Human recombinant IFN alpha 2-b manufactured in/from Eeryhia Coli, at the Center for Genetic Engineering and Biotechnology, in Havana (CIGB): 3, 5, 6, or 10 x 106

Other ingredients:

Benzyl alcohol, polysorbate 80, sodium chloride, sodium phosphate as a bumper? (buffer system)

The day of the 2014-15 world

Antiviral, antiproliferative, immunomodulator, antisngiogeno, antifibrotic

Indications:

The use of HEBERON ALFA R is useful for patients under the following pathological circumstances:

VIRAL DISEASES

Infections caused by human papilloma virus

In recurrent respiratory papillomatosis (RRP), the use of recombinant IFN alpha-2b (CIGB) as adjuvant surgery has shown satisfactory results. Treatment of IFN alf, can cause partial or complete remission of papillomas. In Cuba, however, it is intended for use in the prevention of recurrence of the disease after surgical removal of the tumor. Since 1983, for this purpose, the program has been realized in cases with papilloma on the larynx. Since 1994, this program has continued, including papillomatosh lesions throughout the respiratory tract. The efficacy of the IFN alpha 2-b recombinant (CIGB) was demonstrated in Condylomata accuminate in a controlled double-blind study, combining systemic treatment with topical application of 20 000 IU/g IFN alpha 2-b in hydrophilic cream.

Viral hepatitis

The use of IFN alpha 2-b (CIGB) in subacute liver necrosis by intraperitoneal and intramuscular pathway increases the likelihood of patient survival and promotes histological healing. In chronic hepatitis B with a positive “e” antigen, 50% seroconversion can be obtained after a 4-month regimen with recombinant IFN alpha 2-b (CIGB). The treatment is extremely useful in immunosuppressive patients.

HEBERON ALPHA R is also useful for children. Six months after the six-month regimen, 40% of the antigen seroconversion can be achieved. This reaction can be 50% after 3 years of follow up. Histological progress is 69%. HEBERON ALFA R is also useful in chronic hepatitis C, where its efficacy has been demonstrated in several clinical studies. In whole, 80% of enzymatic reaction (ALAT normalization) is reached versus 22% among control groups., 41% of reactions were maintained after 9-month follow-up. In thalassemia patients, who often receive blood transfusions and are therefore a risk group for this disease, HEBERON ALFA R was shown to be effective in 63% negativeization of viral in serum RNA (55% with concomitant normalization of ALT) at 12 months of treatment with 3×106 IU every other day. . Also in patients with chronic renal insufficiency under periodic haemodialysis and chronic hepatitis C , HEBERON ALFA R produced a 75% viral reaction and 87% enzymatic reaction. In combination with ribavirin, the efficacy of treatment with HEBERON ALFA R is increased in chronic hepatitis produced by C virus.

HEBERON ALFA R has also been useful in children – where chronic hepatitis C is less common, and where there are rarely reports in the literature. In acute hepatitis C, the use of HEBERON ALFA R is converted to prevent the development of chronic disease.

Patients infected with human immunodeficiency virus

IFN has an anti-retroviral effect and is considered a limiting factor of human immunodeficiency virus infection. Random tests were performed to prevent or delay the progression of acquired loss syndrome (AIDS) in individuals in the early stages of HIV infection. Long-term treatment with HEBERON with ALPHA R significantly reduces the proportion of individuals who have had some of the symptoms or developed AIDS. Further monitoring of these patients allowed the analysis of survival rates and other long-term complications. It was concluded that the use of HEBERON ALFA R during the early stages of HIV infection, although no other symptoms of AIDS occurred, was also useful for prolonging life.

Dengue

Early application of IFN alfa, during the first 72 hours of infection, serious haemorrhagic (hemorrhoid) complications and shock may be prevented.

NEOPLASIA

Haematopoietic tissue

Hairy cell leukemia: As for other interferon alpha preparations, HEBERON ALFA R causes disease regression or significant clinical stabilisation even if the patient has previously been splenectomised. Hronic myeloid leukaemia: Remission may be achieved using IFN alfa but HEBERON ALFA is recommended to maintain remission previously achieved with haemotherapy. Return is prevented for a year, life is extended and there is a significant decrease in the proportion of chromosomes Philadelphia chromosome + cells. In multiple myeloma, HEBERON ALFA R is used as a maintenance therapy after complete or partial remission with melphalan-prednisone. Non-Hodgkin’s low- and mean malignancy lymphoma : The use of IFN alpha 2-b (CIGB) is recommended in cases where remission is achieved using chemotherapy or radiotherapy. The frequency of relapse was significantly reduced and life-extending was achieved. In skin T-cell lymphoma (Mycosis Fungoide, Sezary’s syndrome and other)the efficacy of treatment with IFN has been demonstrated. High response rate (more than 50%) achieved even after 3 years of follow-up. In addition, most of those who did not respond (non-responders) had stable disease, so the control rate of the disease (without progression) was 95, 91, 90, 82, and 76% through 6, 12, 18, 24, 36 months of follow-up.

Solid tumours

HEBERON ALFA R is used to treat solid tumors that are known indications for this type of product, such as kidney cancer, Kaposhi’s sarcoma (in conjunction with AIDS), basal cell carcinoma, and superficial bladder cancer. In addition, there are tumors that are recognized as indications for IFN alpha, such as malignant melanoma, and carcinoid tumor where HEBARON ALFA R is equally effective. On the other hand, there are results that indicate the efficacy of HEBARON ALFA R in fibroma and haemangioma in babies, which despite the fact that they are benign can have serious consequences per patient.

Basal cell skin cancer:

HEBERON ALFA R is an alternative treatment in cases where surgical resomission is not possible or desirable. 90% of objective response was obtained by intrlesia app of 1.5 x 106 IU, 3 times a week for 3 weeks. Patients who responded were left relieved of relapse after a year of follow-up.

Superficial bladder cancer:

HEBARON ALFA R can be used by intravezial implantation as an adjuvant, to prevent the river after surgical removal of the limousium with partial cystectomy or endoscopy. The two-year relapse rate was similar to that obtained with BGG, with less adverse reactions.

Haemangioma in babies:

In a study using HEBARON ALFA R subcutaneously, the overall response rate was 66%. In children under the age of one, 65% had regression and no progressions. During the first months of life, tumors are still in a proliferative phase. Therefore, spontaneous regression is rare, and therefore even stabilization can be considered as a satisfactory result. In patients between 1 January 2014 and 31 December 201 And the 5th and 5th. Goode’s age, regression rate is 83%. Even in patients who were over 5 years of age, there was a 44% reaction to treatment. There was no effect on physical and psychomotor development. The second study was conducted using HEBARON ALPHA R intralesional, 3 x 106 IU, twice a week for 8 months. Tumor regression was achieved in 81% of patients and 19% stable disease. There was no progression. Regression was more common (85%) patients aged between 1 and 3. And five years, in children with no known family history of hemagiomas and tumors at birth.

Kaposhi sarcoma (aids related):

HEBARON ALFA R is used as a treatment in this tumor. Complete remission can be achieved after 12-24 months of treatment. An intra-eelic application can be used.

Renal cancer:

Metastatic renal carcinoma is one of the known indications of IFN alpha 2-b. Two reports of patients treated with recombinant HEBERON ALPHA R have been conducted. These include cases with metastatic disease or those that have been operated on and IFN has been used as adjuvant surgery/surgery, as a maintenance therapy. During the first series, 55% target response and 33% disease stabilization were given. The response to therapy or stabilization lasted more than 18 months in 50% of them. In another study, recombinant IFN alpha 2-b (CIGB) was used in combination with hemotherapy, in cases of metastsis or advanced irreperiable tumor. Extended life (42 months) was achieved in one case. On the other hand, in cases where HEBERON ALFA R used post-nephrectemia or after conservative tumor surgery, the survival average was more than 40 months, and more than 50% of patients lived longer than 5 years.

Pejroni’s disease:

In a study where HEBERON ALFA R was conducted intralexically, 1 ml with 10 x 106 IU, twice a week to total lesion regression or up to 14 weeks, the complete clinical response was obtained in 47% of patients. Sexual dysfunction disappeared in 79% of patients who suffered from it, palpable lesions disappeared in 62% of them, erectile sex at 47%, and pain in 94%. The imagenological response rate was 88%; of which 53% is complete response. The main systemic adverse reaction observed was the expected pseudo-influenza syndrome (mild or umeren). The main locally harmful reaction was the formation of a small hematoma, edema, cysts in two patients and venous fungi in one case.

Contraindications:

Hu-r aplfa-2b IFN is contraindicated in patients with hypersensitivity to alpha interferon, benzyl alcohol, polysorbate 80, or to any salts present in preparation.

WARNINGS AND PRECAUTIONS WHEN USING

Although no direct carditoxic effect for HEBERON ALFA R has been described, it is possible that some of its side effects (e.g., fever, tremor, malaise) exacerbate previous cardiac change. Since one of the toxic effects of HEBERON ALFA R may be leukopenia, care should be taken in patients with myelosuppression. Since the kidney is the place where IFN alpha is eliminated, account should be taken when HEBARON ALFA R is used in patients with impaired renal function. Dose reduction should be considered if necessary. The use of different preparations of IFN alfa has been associated with an increase in allergy and autoimmune disorders such as bronchoconstriction, lupus erythematosus, psoriasis, atopic dermatitis, myasthenia gravis, or thyroiditis. These changes are rarely reported/reported when using HEBERON ALFA R. However, it should be taken into account when used in patients with a history of these diseases. Adverse reactions due to HEBERON ALFA R are reversible. In case of severe adverse reactions, the dose should be self-doseed or used. In accordance with the patient’s status, adequate measures should be taken. The general experience is that the intensity of side effects ,due to HEBERON ALFA R, tends to decline as treatment continues. However, this should still be closely monitored.

Carcinogenicity

There is no evidence, experimental or in the literature indicating any carcinogenic potential of IFN alpha. On the contrary, IFN alpha -2b (CIGB) exhibits opposite effects, promoteing cell differentiation in transformed cell lines and tumors in animals.

Mutagenicity

None of the tests showed or suggested that IFN alpha -2b (CIGB) could be mutagenic. This includes Ames’ test with different strains and a test with human lymphocytes in the culture, looking for lame-ass defects.

Teratogenesis or effects on fertility

Rat tests showed no teratogenic reaction or effect on fertility, due to IFN alpha-2b (CIGB).

Pregnancy

There are no controlled studies on the use of HEBERON ALFA in pregnant women. As a result, it has not been determined whether it is safe to use it during pregnancy. If a pregnant woman has indications, the doctor should perform a risk-benefit analysis for each person individually.

Use in pediatrics:

HEBERON ALFA R has been used in children with viral hepatitis C and papillomatose larynx and periodic respiratory papillomatose , benign and malignant neoplasia. Side effects are similar to those in adults , mainly fever and malaise. No changes in growth or psychomotor development were reported, even months after treatment. This product contains benzyl alcohol and should not be used on newborns.

Adverse reactions

HEBERON ALPHA R

The main adverse reactions occurring with the use of HEBERON ALFA R are similar to those reported for other IFN alpha preparations. These adverse reactions are dose dependent and reversible. Their intensity is generally mild (do not require treatment) or directed (reacting to symptomatic treatment) Patients receiving doses ≥6 x 106 IU may have serious reactions requiring additional measures, hospitalization, prolonged hospitalization or suspension treatment. Adverse reactions reported by 809 patients from various clinical studies were listed in the table below., isolated cases with mild allergic reactions (rash, itch), hair loss and cardiovascular toxicity have also been reported.

Frequency of major undesirable effects after use of HEBERON ALFA

Analysis of 809 patients from different clinical studies.

The pharmacovigilance of heberon alfa R use in patients with haematological diseases , mainly chronic myeloid leukaemia, showed a similar profile of adverse reactions. This report includes a case with hemolytic anemia, seemingly after the development of anti-erythrocytes of autoanticell.

Immunegenicity HEBERON ALFA R

Recombinant IFN alpha preparations are immunogenic in variable proportions of patients treated with them. Antibodies can neutralize IFN activity and can therefore prevent or regain response to treatment. The immunogenicity of HEBERON ALFA R has been observed through various clinical studies conducted with this product. OF THE 563 patients treated with HEBERON ALFA R, whose serums were evaluated/evaluated, 14 (2.5%) anti IFN alpha neutral activity. Conclusion, different studies and adverse reactions observed during HEBERON ALFA R therapy show a similar profile of adverse reactions than those reported for other preparations containing IFN alpha 2-b as an active principle.

Interactions with other medicinal products and other forms of interaction

HEBERON ALFA R has synergistic effect with some anti-tumor drugs, in connection with their antiproliferative effects, which must be considered in combination therapy, since the effects of myelosuppression are also intensified. It also shows/indicates synergism, both antiproliferative and anti-…… (not seen on paper) with interferon gam. Drug-doseing studjia Adverse reactions to HEBERON ALFA R depend on the dose. At doses greater than 10 x 106 IU/m2 of the surface of the court, the same unwanted effects, although more intense, are obtained . asthenia and depression are described at high doses. These deeds are reversible.

Posology and forms of administration

The usual dose in adults is 3 to 6 x 106 IU. In some special situations in cancer patients , higher doses can be used, bearing in mind that unwanted effects will be more intense. In children, the usual dose is 3 to 6 x 106 IU/m2 of the surface of the surface. The frequency of the application varies from one daily to three times, twice or once a week. The last two options are more used in extended treatment regimens (prolonged tretment schedules). The administration mode is intramuscular or subcutaneous. However, intravenous, intratraheal, intralezional and intraperitoneal modes are also possible.

Use code:

HEBERON ALPHA R

Periodic respiratory papillomatosis

After surgical removal of lesions, the following regimen is recommended:

TPW: times a week

Condialation of acuminates

6×106.3 times a week, intramuscularly, for 6 weeks, combined with topical application of the cream containing IFN alfa, (20 000 IU/g), three times a day.

Viral hepatitis

Subacute hepatitis: 12 to 15 x 106UI for 3 to 5 days, intraperitoneal or intramuscular route, followed by 6 x 106 IU intramuscularly every other day. Treatment should continue until the normalization of viral markers and markers of the disease.

Acute hepatic insufficiency in babies: 3 to 6 x 106 IU/m2 per day intraperitoneal for one week. The second week the same dose is used intramuscularly. Based on the patient’s evolution, the frequency of the application can be reduced to 3 times a week from the third week onwards. Treatment should continue until the normalization of viral markers and markers of the disease.

Subacute (subfulminant) viral hepatitis in children older than one year of age: 3 to 6 x 106 IU for one or two weeks, intraperitoneal route during the first week, and thereafter intramuscularly. Tretma can be continued at the same dose 3 times a week, in accordance with viral markers and clinical status of the patient.

Chronic hepatitis B

In adults 6 x106 IU daily intramuscularly for 2 weeks, then 3 times a week for 4 weeks and twice a week for 16 weeks. In children 3 to 6 x106 IU/m2 intramuscularly, 3 times a week for 16 weeks. If the child is over 12 years of age, the dose should be 6 x106 IU.

Chronic hepatitis, non A, non B, C positive: 3 x 106 IU intramuscular or subcutaneous., 3 x weekly for 9 months. The efficiency of the treatment is increased if combined with ribavirin , 200-400mg, 3 times a day over the same period of time.

Human immunodeficiency virus of infected subjects: 3 x 106 IU, 3 times a week during the asymptomatic period . This treatment should be long-term, with haematological and anti IFN antithetics monitoring. In patients with Kaposhi sarcoma, a higher dose of up to 30 x 106 IU/m2 per day is recommended, as with other IFN alpha preparations. However, in cases where diagnosis is set early, IFN alpha 2-b (CIGB) has caused total remission at 6 x 106 IU over 6 to 12 weeks.

Dengue

IFN alfa 2-b (CIGB) should be used earlier/before the expiration of 72 hours of symptoms. In children, 50 to 100,000 IU/Kg weight, daily for 3 days. In adults, 3 to 6 x 106 IU at the same frequency.

Hyonic myeloid leukaemia

Once haematological remission is achieved, IFN alpha-2b (CIGB) can be given every other day, at 3 x 106 IU/m2 cytogenetic remission , a bone marrow transplant can be done. Or disease progression occurs.

Non Hočkinov lymphoma of low and medium degree malignancy

After receiving remission with polyemotherapy, 6 x 105 IU 3 times a week for a year or more, to disease progression.

Skin basal cell carcinoma

*In patients where surgical lesion removal is not possible or desirable, 1.5 x 106 IU, intralezionally, 3 times a week for 3 weeks.

Superficial urinary bladder cancer

Intravezial instillation of 20 x 106 IU recombinant IFN alfe-2b (CIGB) in 50 ml, weekly for 8 weeks and then monthly for 2 years

Haemangioma in newborns

In tumours larger than 2 cm, 3 x 106 IU/m2, subcutaneously, daily for 6 months and then 3 times a week for about 12 months. The same dose can be administered intralezionally, twice a week, if the tumour is well branched.

Malignant melanoma

After surgery, in patients who do not have lesions (lesion free) but with the risk of relapse, 20 x 106 IU intravenously or intramuscularly, 5 days in a row weekly, for 4 weeks, then 10 x 106 IU 3 times a week to one year.

Pejroni’s disease

Jedam ml containing 10 x 10 6 IU, intralezionally, twice a week for 14 weeks or less if there is a complete response to therapy before that.

Storage conditions

The vials should be stored on a tempreature of 2 to 8 ◦C.

Presentation/View

HEBERON ALFA R is a liquid (3M, 5M, 6M and 10M) presented in one, 10 or 25 vials and thermal cases with one vial and syringe.

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