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INTRON A（interferon alfa-2b） injection, solution

2014-01-07 00:15:57 来源: 作者: 【大中小】浏览:411次评论:0条

INTRON A - interferon alfa-2b
INTRON A - interferon alfa-2b injection, solution
Schering Corporation
INTRON® A
Interferon alfa-2b, recombinant
For Injection

PRODUCT INFORMATION

WARNING

Alpha interferons, including INTRON® A, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory eva luations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping INTRON A therapy. See WARNINGS and ADVERSE REACTIONS.

DESCRIPTION

INTRON® A (Interferon alfa-2b) for intramuscular, subcutaneous, intralesional, or intravenous Injection is a purified sterile recombinant interferon product.

INTRON A recombinant for Injection has been classified as an alpha interferon and is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon alfa-2b gene from human leukocytes. The fermentation is carried out in a defined nutrient medium containing the antibiotic tetracycline hydrochloride at a concentration of 5 to 10 mg/L; the presence of this antibiotic is not detectable in the final product. The specific activity of interferon alfa-2b, recombinant is approximately 2.6 × 108 IU/mg protein as measured by the HPLC assay.

Powder for Injection
Vial Strength Million IU	mL Diluent	Final Concentration after Reconstitution million IU/mL*	mg INTRON A† per vial	Route of Administration
* Each mL also contains 20 mg glycine, 2.3 mg sodium phosphate dibasic, 0.55 mg sodium phosphate monobasic, and 1.0 mg human albumin. Based on the specific activity of approximately 2.6 × 108 IU/mg protein, as measured by HPLC assay. †
10	1	10	0.038	IM, SC, IV, IL
18	1	18	0.069	IM, SC, IV
50	1	50	0.192	IM, SC, IV

Prior to administration, the INTRON A Powder for Injection is to be reconstituted with the provided Diluent for INTRON A (Sterile Water for Injection USP) (see DOSAGE AND ADMINISTRATION). INTRON A Powder for Injection is a white to cream-colored powder.

Solution Vials for Injection
Vial Strength	Concentration*	mg INTRON A† per vial	Route of Administration
* Each mL contains 7.5 mg sodium chloride, 1.8 mg sodium phosphate dibasic, 1.3 mg sodium phosphate monobasic, 0.1 mg edetate disodium, 0.1 mg polysorbate 80, and 1.5 mg m-cresol as a preservative. † Based on the specific activity of approximately 2.6 × 108 IU/mg protein as measured by HPLC assay. ‡ This is a multidose vial which contains a total of 22.8 million IU of interferon alfa-2b, recombinant per 3.8 mL in order to provide the delivery of six 0.5-mL doses, each containing 3 million IU of INTRON A (for a label strength of 18 million IU). This is a multidose vial which contains a total of 32.0 million IU of interferon alfa-2b, recombinant per 3.2 mL in order to provide the delivery of five 0.5-mL doses, each containing 5 million IU of INTRON A (for a label strength of 25 million IU). §
18‡ MIU multidose	3 million IU/0.5 mL	0.088	IM, SC
25§ MIU multidose	5 million IU/0.5 mL	0.123	IM, SC, IL

Solution in Multidose Pens for Injection
Pen Strength	Concentration* Million IU/1.5ml	INTRON A Dose Delivered (6 doses, 0.2 mL each)	mg INTRON A† per 1.5 mL	Route of Administration
* Each mL also contains 7.5 mg sodium chloride, 1.8 mg sodium phosphate dibasic, 1.3 mg sodium phosphate monobasic, 0.1 mg edetate disodium, 0.1 mg polysorbate 80, and 1.5 mg m-cresol as a preservative. Based on the specific activity of approximately 2.6 × 108 IU/mg protein as measured by HPLC assay. †
3MIU	22.5	3 MIU/0.2ml	0.087	SC
5 MIU	37.5	5 MIU/0.2ml	0.144	SC
10 MIU	75	10 MIU/0.2ml	0.288	SC

These packages do not require reconstitution prior to administration (see DOSAGE AND ADMINISTRATION). INTRON A Solution for Injection is a clear, colorless solution.

CLINICAL PHARMACOLOGY

General

The interferons are a family of naturally occurring small proteins and glycoproteins with molecular weights of approximately 15,000 to 27,600 daltons produced and secreted by cells in response to viral infections and to synthetic or biological inducers.

Preclinical Pharmacology

Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Once bound to the cell membrane, interferons initiate a complex sequence of intracellular events. In vitro studies demonstrated that these include the induction of certain enzymes, suppression of cell proliferation, immunomodulating activities such as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells, and inhibition of virus replication in virus-infected cells.

In a study using human hepatoblastoma cell line HB 611, the in vitro antiviral activity of alpha interferon was demonstrated by its inhibition of hepatitis B virus (HBV) replication.

The correlation between these in vitro data and the clinical results is unknown. Any of these activities might contribute to interferon's therapeutic effects.

Pharmacokinetics

The pharmacokinetics of INTRON® A were studied in 12 healthy male volunteers following single doses of 5 million IU/m2 administered intramuscularly, subcutaneously, and as a 30 minute intravenous infusion in a crossover design.

The mean serum INTRON A concentrations following intramuscular and subcutaneous injections were comparable. The maximum serum concentrations obtained via these routes were approximately 18 to 116 IU/mL and occurred 3 to 12 hours after administration. The elimination