Ribavirin (Copegus®; Rebetol®; Ribasphere®; Vilona®,Virazole®, also generics from Sandoz, Teva, Warrick) is an anti-viral drug which is active against a number of DNA and RNAviruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of viral genetic material. Though not effective against all viruses, ribavirin is remarkable as a small molecule for its wide range of activity, including important activities against influenzas, flaviviruses and agents of many viral hemorrhagic fevers.
Ribavirin is a pro-drug, 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. A number of mechanisms have been proposed for this (see Mechanisms of Action, below) but none of these is proven. More than one mechanism may be active.
In the U.S. the oral (capsule or tablet) form of ribavirin is used in the treatment of hepatitis C, in combination with interferon drugs. The aerosol form is used to treat respiratory syncytial virus-related diseases in children. In Mexico, ribavirin ("ribavirina") has been sold for use against influenza.
The primary serious adverse effect of ribavirin is hemolytic anemia, which may worsen preexisting cardiac disease. The mechanism for this effect is unknown. It is dose-dependent and may sometimes be compensated by decreasing dose.
Ribavirin is not substantially incorporated into DNA, but does have a dose-dependent inhibiting effect on DNA synthesis, as well as having other effects on gene-expression. Possibly for these reasons, significant teratogenic effects have been noted in all non-primate animal species on which ribavirin has been tested. Ribavirin did not produce birth defects in baboons, but this should not be an indication that it is safe in humans. Therefore, two simultaneous forms of birth control are recommended during treatment of either partner and continued for six months after treatment. Women who are pregnant or planning to become pregnant are advised to not take ribavirin. Of special concern as regards teratogenicity is the ribavirin's long half-life in the body. Red blood cells (erythrocytes) concentrate the drug and are unable to excrete it, so this pool is not completely eliminated until all red cells have turned over, a process estimated to take as long as 6 months. Thus in theory, ribavirin might remain a reproductive hazard for as long as 6 months after a course of the drug has ended. Drug packaging information materials in the U.S. now reflect this warning.
Oral ribavirin, as Rebetol®, was marketed in the U.S. till 2005 by Schering Plough with royalty payments for licensing made to Valeant Pharmaceuticals International (see History below). It was also marketed as Copegas ® tablets by Roche Pharmaceuticals under a separate license to Valeant Pharmaceuticals International. After concluding patent disputes over generic ribavirin availability in 2003, Three Rivers Pharmaceuticals, LLC in conjunction with Par Pharmaceutical, was approved in 2005 to market ribavirin as Ribosphere® capsules. Generic ribavirin (200 mg, no brand name) became available in 2005 from Sandoz, Teva Pharmaceutical Industries, and Warrick Pharmaceuticals, which is the generic arm of Schering Plough. More generics are expected, including one from Geneva. These products are expected to displace the brand name products paying license fees to Valeant Pharmaceuticals International. The only present FDA-approved indication for these products is in conjunction with interferon against chronic hepatitis C with hepatic damage.
In Mexico, oral ribavirin has been available since the 1980's as an over-the-counter drug ("ribavirina," ICN pharmaceuticals Spanish tradename Vilona®), for treating influenza. In this form it was occasionally brought into the U.S. for HIV/AIDS patients. However, ribavirin has proven to have little if any clinical usefulness against HIV, and it can greatly increase blood levels and also toxicity of the HIV antiviral didanosine (ddI, Videx®). Other interactions with nucleoside antivirals for HIV should be considered when HIV/AIDS patients use ribavirin to treat hepatitis C (see "aidsinfo" external link).
