1. Interferon beta-1b (DB00068) Approved Drug
Chemical Formula: C908H1408N246O253S6
Molecular Weight:20011
Human interferon beta (165 residues), cysteine 17 is substituted with serine. Produced in E. coli, no carbohydrates, MW=18.5kD
Indication/Usage
Interferon beta-1b is a drug used for the treatment of relapsing/remitting multiple sclerosis. It has been shown to slow the advance of the disease as well as to decrease the frequency of attacks.
Pharmacodynamics
Interferon beta upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin, neopterin and protein kinase R.

2. Volume of Distribution
Mechanism Of Action
Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon beta binds more stably to type I interferon receptors than interferon alpha.
Volume of Distribution
* 0.25 to 2,88 L/kg
Clearence
* 9.4 – 28.9 mL/min•kg-1 [patients with diseases other than MS receiving single intravenous doses up to 2.0 mg]
Category
Adjuvants, Immunologic and Immunosuppressive Agents
Affected Organisms
Human and other Mammals
Patents
Patent no , Canada, approved: expired:
Patent no , Canada, approved: expired:
Drug Interactions
DB00495 (Zidovudine): The interferon increases the effect and toxicity of zidovudine
Sequence
MSYNLLGFLQRSSNFQSQKLLWQLNGRLEYCLKDRMNFDIPEEIKQLQQFQKEDAALTIYEMLQNIFAIFRQDSSSTGWNETIVENLLANVYHQINHLKTVLEEKLEKEDFTRGKLMSSLHLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINRLTGYLRN

3. Experimental Properties
Hydrophobiity: 0.447
Isoelectric Point: 9.02
Targets
Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2
Brands
Betaseron – Bayer
Betaferon – Bayer
Extavia – Novartis

4. Betaseron Formulation Used/Prescribed for Dosage Contraindications
Betaseron® (interferon beta-lb) is a purified, sterile, lyophilized protein product produced by recombinant DNA techniques. Interferon beta-1b is manufactured by bacterial fermentation of a strain of Escherichia coli that bears a genetically engineered plasmid containing the gene for human interferon betaser17 . The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta-1b has 165 amino acids and an approximate molecular weight of 18,500 daltons. It is sterile, white to off-white powder for subcutaneous injection
Formulation
Each vial contains 0.3 mg of interferon beta-lb. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.
Used/Prescribed for
Betaseron is used to treat relapsing multiple sclerosis (MS). Betaseron will not cure MS, it will only decrease the frequency of relapse symptoms.
Dosage
The recommended starting dose is mg (0.25 mL) subcutaneously every other day, with dose increases over a six week period to the recommended dose of 0.25 mg (1 mL) every other day.
Contraindications
Betaseron is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, Albumin (Human).

5. Side-effects Drug Interactions References
depressed mood, anxiety, trouble sleeping, restlessness, or thoughts of suicide or hurting yourself; bruising, swelling, oozing, or skin changes where the injection was given;weight changes, pounding heartbeats, feeling too hot or cold; fever, chills, body aches, flu symptoms; or nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). Less serious Betaseron side effects may include: weakness; headache; muscle pain or weakness; sleep problems (insomnia); stomach pain; swelling in your hands or feet; skin rash; or irregular menstrual periods.
Drug Interactions
A total of 414 drugs (2122 brand and generic names) are known to interact with Betaseron (interferon beta-1b).
15 major drug interactions (68 brand and generic names)
397 moderate drug interactions (2048 brand and generic names)
2 minor drug interactions (6 brand and generic names)
References

6. Betaferon Formulation Used/Prescribed for Dosage
Betaferon (interferon beta-1b) is a type of medicine known as an interferon, which is used to treat MS. Interferons are proteins found naturally in the body, which may help boost the immune system and fight infections. Betaferon belongs to a class of medicines called disease modifying therapies (DMTs). Betaferon may change the course of your MS. It helps to reduce the frequency, severity and duration of any relapses you may have and can help to slow down the progression of the disease. It has been taken by people with MS for more than 16 years, and there is a wealth of data showing both its effectiveness and safety profile in a broad range of people. It is a powder and solvent that are made upto make solution.
Formulation
Each vial contains 0.3 mg of interferon beta-lb. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.
Used/Prescribed for
Betaferon is indicated for the treatment of
patients with a single demyelinating event with an active inflammatory process, if it is severe enough to warrant treatment with intravenous corticosteroids, if alternative diagnoses have been excluded, and if they are determined to be at high risk of developing clinically definite multiple sclerosis;
patients with relapsing-remitting multiple sclerosis and two or more relapses within the last two years;
patients with secondary progressive multiple sclerosis with active disease, evidenced by relapses.
Dosage
The recommended starting dose is mg (0.25 mL) subcutaneously every other day, with dose increases over a six week period to the recommended dose of 0.25 mg (1 mL) every other day.

7. Contraindications Side-effects References
People with severe depression or thoughts of suicide, People with severe liver disease. In females during Pregnancy, Breastfeeding.
Side-effects
The most frequently observed side-effects are:
Flu-like symptoms- such as fever,chills, painful joints, malaise, sweating, headache or muscular pain. These symptoms may be reduced by taking paracetamol or steroidal anti-inflammatory medicines such as ibuprofen.
Injection site reactions. - Symptoms can include redness, swelling, discolouration, inflammation and pain. These may be reduced by the use of an auto-injector device
References

8. Extavia Formulation Used/Prescribed for Dosage Containdications
EXTAVIA® (interferon beta-1b) is a purified, sterile, lyophilized protein product produced by recombinant DNA techniques. Interferon beta-1b is manufactured by bacterial fermentation of a strain of Escherichia coli that bears a genetically engineered plasmid containing the gene for human interferon betaser17. The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta-1b has 165 amino acids and an approximate molecular weight of 18,500 daltons. It does not include the carbohydrate side chains found in the natural material. EXTAVIA contains the same active ingredients as other interferon beta-1b products. For this reason, these products should not be given concomitantly. It is sterile, white to off-white powder for subcutaneous injection
Formulation
Each vial contains 0.3 mg of interferon beta-1b. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.
Used/Prescribed for
Extavia is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.
Dosage
The recommended starting dose is mg (0.25 mL) subcutaneously every other day, with dose increases over a six week period to the recommended dose of 0.25 mg (1 mL) every other day
Containdications
Extavia is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, Albumin (Human)

9. Side-effects Drug Interactions References
depressed mood, anxiety, trouble sleeping, restlessness, or thoughts of suicide or hurting yourself; bruising, swelling, oozing, or skin changes where the injection was given; weight changes, pounding heartbeats, feeling too hot or cold; fever, chills, body aches, flu symptoms; or nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). Less serious Extavia side effects may include: weakness; headache; muscle pain or weakness; sleep problems (insomnia); stomach pain; swelling in your hands or feet; skin rash; or irregular menstrual periods.
Drug Interactions
A total of 414 drugs (2122 brand and generic names) are known to interact with Extavia (interferon beta-1b).
15 major drug interactions (68 brand and generic names)
397 moderate drug interactions (2048 brand and generic names)
2 minor drug interactions (6 brand and generic names)
References