Rebetron (Schering-Plough)

Rebetron (Schering-Plough) - General Information

Ribavirin is an anti-viral drug which is active against a number of DNA and RNA viruses. It is a nucleoside antimetabolite. Ribavirin actually functions as a pro-drug, which is activated by cellular kinases which change it into the 5' triphosphate nucleotide. In this form it interferes with aspects of RNA metabolism related to viral reproduction. Intron A is an alpha interferon 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. It is used for the treatment of Hepatitis B and C. Interferons are a family of naturally occurring small proteins and glycoproteins produced and secreted by cells in response to viral infections and to synthetic or biological inducers. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface.

Pharmacology of Rebetron (Schering-Plough)

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. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Rebetron (Schering-Plough) for patients

Combination REBETOL/ INTRON A therapy must not be used by women who are pregnant or by men whose female partners are pregnant. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients taking combination REBETOL/ INTRON A therapy. Combination REBETOL/ INTRON A therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Patients must perform a pregnancy test monthly during therapy and for 6 months posttherapy. Women of childbearing potential must be counseled about use of effective contraception (two reliable forms) prior to initiating therapy. Patients (male and female) must be advised of the teratogenic/ embryocidal risks and must be instructed to practice effective contraception during combination REBETOL/ INTRON A therapy and for 6 months posttherapy. Patients (male and female) should be advised to notify the physician immediately in the event of a pregnancy.

If pregnancy does occur during treatment or during 6 months posttherapy, the patient must be advised of the significant teratogenic risk of REBETOL therapy to the fetus. Patients, or partners of patients, should immediately report any pregnancy that occurs during treatment or within 6 months after treatment cessation to their physician. Physicians are encouraged to report such cases by calling (800) 727-7064.

Patients receiving combination REBETOL/ INTRON A treatment should be directed in its appropriate use, informed of the benefits and risks associated with treatment, and referred to the patient MEDICATION GUIDE. There are no data evaluating whether REBETOL/ INTRON A therapy will prevent transmission of infection to others. Also, it is not known if treatment with REBETOL/ INTRON A therapy will cure hepatitis C or prevent cirrhosis, liver failure, or liver cancer that may be the result of infection with the hepatitis C virus.

If home use is prescribed, a puncture-resistant container for the disposal of used syringes and needles should be supplied to the patient. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes. The full container should be disposed of according to the directions provided by the physician.

The most common adverse experiences occurring with combination REBETOL/ INTRON A therapy are "flu-like" symptoms, such as headache, fatigue, myalgia, and fever and appear to decrease in severity as treatment continues. Some of these "flu-like" symptoms may be minimized by bedtime administration of INTRON A therapy. Antipyretics should be considered to prevent or partially alleviate the fever and headache. Another common adverse experience associated with INTRON A therapy is thinning of the hair.

Patients should be advised that laboratory evaluations are required prior to starting therapy and periodically thereafter. It is advised that patients be well hydrated, especially during the initial stages of treatment.

Rebetron (Schering-Plough) Interactions

Rebetron (Schering-Plough) Contraindications

Combination REBETOL/INTRON A therapy must not be used by women who are pregnant or by men whose female partners are pregnant. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients taking combination REBETOL/INTRON A therapy. Combination REBETOL/INTRON A therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has been concluded. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL Capsules. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment s.o.s. physicians are encouraged to report such cases by calling (800) 727-7064.

REBETOL Capsules in combination with INTRON A Injection is contraindicated in patients with a history of hypersensitivity to ribavirin and/or alpha interferon or any component of the capsule and/or injection.

Patients with autoimmune hepatitis must not be treated with combination REBETOL/INTRON A therapy.

Additional information about Rebetron (Schering-Plough)

Rebetron (Schering-Plough) Indication: For treatment of Hepatitis C
Mechanism Of Action: Ribavirin is readily phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is a potent competitive inhibitor of inosine monophosphate (IMP) dehydrogenase, viral RNA polymerase and messenger RNA (mRNA) guanylyltransferase (viral). Guanylyltranserase inhibition stops the capping of mRNA. These diverse effects result in a marked reduction of intracellular guanosine triphosphate (GTP) pools and inhibition of viral RNA and protein synthesis. Ribavirin is also incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity. Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, 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 alpha binds less stably to type I interferon receptors than interferon beta.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Ribavirin and Alfa Interferon (Intron A)
Synonyms: Interferon alpha-2 precursor; Interferon alpha-A; LeIF A
Drug Category: Coagulants; Thrombotic Agents
Drug Type: Biotech; Approved

Other Brand Names containing Ribavirin and Alfa Interferon (Intron A): Rebetron (Schering-Plough);
Absorption: Not Available
Toxicity (Overdose): Not Available
Protein Binding: Not Available
Biotransformation: Not Available
Half Life: Not Available
Dosage Forms of Rebetron (Schering-Plough): Not Available
Chemical IUPAC Name: Not Available
Chemical Formula: C860H1353N229O255S9
Ribavirin and Alfa Interferon (Intron A) on Wikipedia: Not Available
Organisms Affected: Humans and other mammals