Ribavirin

An anti-viral drug indicated for severe RSV infection, hepatitis C infection in conjunction with peginterferon alfa-2b or peginterferon alfa-2a, and other antiviral drugs, and other viral infections.

A prodrug, which when metabolized resembles purine RNA nucleotides.

In this form it interferes with RNA metabolism required for viral replication.

Bioavailability 45% oral without food, about 76% with food.

Half-life 12 days – Multiple Dose; 120-170 hours – Single Dose

Excretion 10% fecal, remainder in urine with 30% unchanged, with the remainder metabolites.

Brand names: Copegus, Rebetol, Ribasphere, Vilona, and Virazole.

Primary observed serious adverse side effect is hemolytic anemia, which may worsen preexisting cardiac disease.

The drug buildups up inside erythrocytes.

Causes reduced ATP levels and glutathione levels permitting oxidative damage to erythrocyte cell membrane.

The hemolytic anemia is dose-dependent.

Hemolysis may be compensated by decreasing dose.

Active against a number of DNA and RNA viruses.

A nucleoside antimetabolite drug that interferes with duplication of viral genetic material.

Ribavirin is active against influenzas, and flaviviruses.

Useful for many viral hemorrhagic fevers.

Oral form is used in the treatment of hepatitis C, in combination with pegylated interferon drugs.

Only known treatment viral hemorrhagic fevers, including Lassa fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection.

Used to control enterovirus 71 which causes hand, foot, and mouth disease.

Has been used as a treatment for herpes simplex virus, reducing the severity of outbreak and promoted recovery.

Can increase blood levels of the HIV antiviral didanosine (ddI, Videx).

Suspected that it requires RNA-dependent enzymes for its antiviral activity.

When ribavirin is incorporated into RNA, as a base analog of either adenine or guanine, uracil or cytosine, ii induces mutations in RNA-dependent replication in RNA viruses, and such hypermutation can be lethal to RNA viruses.

Ribavirin 5′ mono- di- and tri-phosphates are all inhibitors of some viral RNA-dependent RNA polymerases essential to the replication cycle of RNA viruses.

Oral absorption is about 45%, and this is increased to about 75% by a fatty meal.

Widely distributed in all tissues, including the CSF and brain.

Trapping of the phosphate form inside cells, particularly red blood cells (RBCs), results in high intracellular concentrations of the drug.

Kinase activity converts the drug to active nucleotide form, is provided by adenine kinase, which is more active in virally infected cells.

The mean half-life for multiple doses in the body is about 12 days.

RBCs store ribavirin for the lifetime of the cells.

One third of absorbed ribavirin is excreted into the urine unchanged.

The remaining drug is excreted into urine as the de-ribosylated base 1,2,4-triazole 3-carboxamide, and the hydrolysis product of this, 1,2,4-triazole 3-carboxylic acid.

Not substantially incorporated into DNA, but has a dose-dependent inhibiting effect on DNA synthesis. Women who are pregnant or planning to become pregnant are advised not to take because of possible teratogenicity.

Should not be given with zidovudine because of the increased risk of anemia.

Concurrent use with didanosine should likewise be avoided because of an increased risk of mitochondrial toxicity.

Routes of administration include: liquid for inhalation, capsules and tablets.

Dosage based on ody weight and renal function.

< 47 kg 1 5 mg/kg/day 47-59 kg- 800 mg/day 2 x 200 mg capsules bid 60-73 kg -1000 mg/day 2 x 200 mg capsules A.M. and 3 x 200 mg capsules P.M. > 73 kg -1200 mg/day 3 x 200 mg capsules A.M. and 3 x 200 mg capsules P.M.