Gene Recombinant Interferon α(alpha)-2b for Injection

1. Description

rInterferon is a kind of E.coli-derived recombinant human Interferon α-2b for injection which is a highly purified by advanced Monoclonal Antibody Affinity Chromatograph technology .

It has 166 amino acid residues and a molecular weight of 19KD.Besides the additional Methionine on its NH2-terminus,the amino acid sequence of rInterferon is identical to that of natural HuIFN α-2b.

rInterferon is highly purified preparation. The excellent quality is strongly ensured because an advanced Monoclonal Antibody Affinity Chromatography technology,was applied in protein purification.

rInterferon is a sterile,white,lyophilized powder for administration after reconstitution with  1ml Bacteriaostatic water for Injection per vial. The reconstituted product is nearly isotonic and has a pH of approximately 7.0 ,the activity of rInterferon Injection is expressed in terms of International Units (IU),with 1 million IU corresponding to 8 microgram of rHuIFN α-2b protein. International Units are determined by comparison of the activity of rInterferon with the activity of the international reference preparation of human leukocyte Interferon established by World Health Organization(WHO).Activities are measured by quantitative assay of WISH cell growth after VSV attach.Each vial of rInterferon contains either 1 million,3 million IU of rHuIFN α-2b;aslo,sodium phosphate dibasic and sodium phosphate dibasic and sodium phosphate monobasic as buffering agents;human albumin as a stabilizer.

2.Clinical Pharmacology

General

Clinical testing and application have demonstrated that recombinant human Interferon have significant therapeutical effect on more than 30 kinds of important human diseases which include viral infection and tumor. Action that have been demonstrated for human Interferon include.

A.Resistance to Virus

Almost all kinds of DNA and RNA virus infection can be interfered by Interferons.The resistance mechanism can be defined as the following complex chain of molecular events:

1)Interferon synthesis induced by specific signal during virus infection.

2)Interferon binds to the receptor on the surface of susceptible cells.

3)Activation of Anti-viral protein(AVP)/or AVP gene expression.

4)Activated AVP can suppress the gene transcription and inhibit the protein translation of virus,then those susceptible cells exhibit resistance to virus.

B. Immunological Enhancement

It is widely acknowledged that Interferon can significantly increase the activities of Nature Killer cells(NK),Killer cells(K)and Macrophage.Interferon αcan alsoenhance the expression level of surface antigen and receptor of immune cells.

C.Resistance to Tumor

Interferons have the ability to show the growth rate of cell,especially of rapid dividing tumor cells.The possible mechanism of resistance to tumor maybe include:

1)Interferon can interact with tumor cells directly,then inhibit its proliferation;

2)As described above ,Interferons can regulate the immunogical function of organism (i.e.enhancement of the activities of NK,K cell and macrophage);

3)iInterferons can suppress the tumor-induced angiogenesis.It should be pointed out that up to now more than 20 kinds of Interferon subtypes have been identified.Different subtypes has different action.For example,IFN α-2b is the most effective on treatment for Chronic Hepatitis B and Chronic Hepatitis C.

Pharmacokinetics

The pharmacokinetics of rINTERFERON has been investigated in health men after the intramuscular administration of 3 million IU. A mean peak concentration(Cmax) of 12  4IU/ml occurred at a mean time of 7 hrs. The mascular pharmacokinetics profile of rInterferon is comparable to results citied in published literature. There is a considerable variability in Pharmacokinetics profile of Interferons,this is due to different subtypes,various dosages and different administration routes.For same subtypes of interferon,a high dosage usually yields a half-life longer than a small one;the Cmax of administration via intramuscular (IM) and subcutaneous (SC)are obviously much lower than that of administration via intraveous(IV),but plasma levels sustained for longer;either IM or SC administration yields similar plasma curves,although the Cmax may be slightly delayed after SC injection.

3.INDICATIONS

rINTERFERON(Recombinant Human Interferon α-2b for Injection)is indicated for the long-term treatment for Chronic Hepatitis B.

rINTERFERON(Recombinant Human Interferon α-2b for Injection) is also indicated for the long-term treatment for Chronic Hepatitis C..

4.ADVERSE REACTIONS

The most commonly adverse reactions were fever.These effects were reversible within 72 hours of interruption of cessation of treatment and were dose-related.Common effects include shivery,arthragia,tiredness and headache.Less common reactions include vomiting,depression,alopecia,nausea,etc. rarely occuring effects include transient rash. Administration of rINTERFERON may also cause leukopenia and thrombocytopenia in some patients. All of those adverse reactions are temporal and tolerable,they often happen at the beginning of therapy,and may be alleviated and disappeared in four weeks.

5.CONTRAINDICATIONS

rINTERFERON should not be used in patients who is hypersensitive to IFN α-2b and other component of this injection.

rINTERFERON SHOULD NOT BE USED TO PREGNANT WOMAN AND NURSING MOTHER. It is remained unknown whether rINTERFERON can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Yet it is not known whether the components of rINTERFERON are excreted in human milk. Because many drugs excreted in milk and because of the potential adverse reactions from rINTERFERON injection in nursing infants,a decision should be made for the mother whether to discontinue nursing or to give up rINTERFERON therapy.

6.WARNINGS andPRECAUTIONS

Although serious,acute hypersensitivity reactions to rINTERFERON injection have not been ovserved ,if such a reaction develops,administration of rINTERFERON should be discontinued immediately.Moderate to severe adverse experiences may require modification of the patient's dosage regimen,or in some case,termination of rINTERFERON injection therapy.Patients suffering heart,liver and kidney trouble should be cautious upon rINTERFERON administration. Experience in patients BELLOW 18 YEARS old of age has been limited and in such cases the expected benefit should be carefully weighed aganist potential hazard. Dose should be reduced when rINTERFERON has to be used in patients under 18,and patients should be monitored.

If the packing bottle of rINTERFERON is demaged,it should be DISCARDED. If rINTERFERON vial is overdue,it should be DISCARDED.The rINTERFERON injuction,if any insoluble substance appears when reconstitute iwth bacteriostatic water,should be DISCARDED. The diluting water should be injected along the bottle wall,then swirl the rINTERFERON vial with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE.

7.DOSAGE AND ADMINISTRATION

Chronic Hepatitis B and Chronic Hepatitis C.

The recommended dosage of rINTERFERON is 3 million IU daily imtramuscular injection in the first two weeks then one another day in the succeeded therapy course.The recommended administration period of rINTERFERON is three months.

The rINTERFERON dosage and administration schedule could be individulized. Higher dose and longer duration of rINTERFERON therapy could be taken under the suggestion of doctor.

8.STABILITY and STORAGE

Before reconstitution. rINTERFERON should be stored 2 ~ 8 ℃ Centidegree (under the refrigeration). AVOID FREEZING THE VIAL OF rINTERFERON.After reconstitution,rINTERFERON should be used immediatedly. Use only one dose per  rINTERFERON vial and discard the unused portion,Expiration dates are stated on the vial labels of rINTERFERON.

9.VIAL SIZE

In vials of  1 Million IU,3 MIU,5 MIU or 10 MIU.

10.SHELF LIFE

Two years.

Product name

Nomenclature:Recombinant Human Interferon α-2b for Injection

Composition

IFN α-2b 10μg,30μg and 50μg  respectively with 10 milligrams of Human Albumin.

Last Updated January 8, 2003

Contact person: Mr.Xu Hai Ke

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