Opegus Capsule

Opegus is indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with other antiviral drugs in patients with compensated liver disease not previously treated with interferon alpha and in adult CHC patients coinfected with HIV. Opegus should not be used alone.

Ribavirin is a synthetic nucleoside which has inhibitory action against respiratory syncytial virus, influenza virus and herpes simplex virus. The mechanism of action is not clear. It may act at several sites including cellular enzymes to interfere with viral nucleic acid synthesis. The mono- and triphosphate derivatives are known to be responsible for the antiviral action of the compound.

The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. After 24 weeks of treatment virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data on treatment for longer than 48 weeks in the previously untreated patient population. In patients who relapse following interferon therapy, the recommended duration of treatment is 24 weeks. There are no safety and efficacy data on treatment for longer than 24 weeks in the relapse patient populations.

Ribavirin + Interferon: Genotype Ribavirin Daily Interferon alpha-2a Duration or interferon alpha-2b.

• All <75 kg: (400+600) mg 3 MIU 3 times weekly 48 weeks Genotypes subcutaneously (Genotype1&4)
• >75 kg: (600+600) mg 24 weeks (Genotype2&3)

Ribavirin + Peg-Interferon: Genotype Ribavirin Daily Peg-Interferon alpha-2a Duration or Peg-interferon alpha-2b:

• 1 & 4 < 75 kg: (400+600) mg 180 gm once weekly 48 weeks
• > 75 kg: (600+600) mg subcutaneously 2 & 3 (400+400) mg 24 weeks

Ribavirin may be administered without regard to food, but should be administered in a consistent manner. Drink plenty of water while being treated with this medication; drinking water will decrease the risk of serious side effects.

Nucleoside reverse transcriptase inhibitors or reduce dose or discontinue interferon, Opegus or both with worsening toxicities

Azathioprine: Concomitant use of azathioprine with Opegus has been reported to induce severe pancytopenia and may increase the risk of azathioprine-related myelotoxicity.

Women who are pregnant. Ribavirin may cause fetal harm when administered to a pregnant woman. Ribavirin is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Patients with hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia). In combination with didanosine. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials.

The most common adverse reactions in adults receiving combination therapy are psychiatric and central nervous system effects, severe ocular disorder, dental and periodontal disorders & growth inhibition in children and adolescents that may be irreversible in some patients. The most common adverse reactions in pediatric subjects were similar to those seen in adults.

Pregnancy Category X. Ribavirin produced significant embryocidal and/or teratogenic effects in all animal species in which adequate studies have been conducted. Malformations of the skull, palate, eye, jaw, limbs, skeleton and gastrointestinal tract were noted. The incidence and severity of teratogenic effects increased with escalation of the drug dose. Survival of fetuses and offspring was reduced.

Nursing Mothers: It is not known whether Ribavirin is excreted in human milk. Because many drugs are excreted in human milk and to avoid any potential for serious adverse reactions in nursing infants from ribavirin, a decision should be made either to discontinue nursing or therapy with Ribavirin, based on the importance of the therapy to the mother.

Birth defects and fetal death with Opegus: Do not use in pregnancy and for 6 months after treatment. Patients must have a negative pregnancy test prior to therapy, use at least 2 forms of contraception and undergo monthly pregnancy tests. For a male patient, it is very important for his female partner to avoid becoming pregnant during treatment and during the 7 months after treatment and do not have sex with a pregnant women.

Pediatric Use: Safety and effectiveness of Opegus in combination with Peginterferon has not been established in pediatric patients below the age of 3 years.

Geriatric Use: The risk of toxic reactions to Opegus may be greater in patients with impaired renal function. The dose of Opegus should be reduced in patients with creatinine clearance less than or equal to 50 ml/min; and the dose of Interferon should be reduced in patients with creatinine clearance less than 30 ml/min.

Hepatic viral infections (Hepatitis C)

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.