Copegus (Ribavirin) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Nucleoside Analogues

NRTIs

In Study NR15961 among the CHC/HIV coinfected cirrhotic patients receiving NRTIs cases of hepatic decompensation (some fatal) were observed (see WARNINGS: Hepatic Failure).

Patients receiving PEGASYS/COPEGUS and NRTIs should be closely monitored for treatment associated toxicities. Physicians should refer to prescribing information for the respective NRTIs for guidance regarding toxicity management. In addition, dose reduction or discontinuation of PEGASYS, COPEGUS or both should also be considered if worsening toxicities are observed (see WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION: Dose Modifications).

Didanosine

Co-administration of COPEGUS and didanosine is not recommended. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials (see CLINICAL PHARMACOLOGY: Drug Interactions).

Zidovudine

In Study NR15961, patients who were administered zidovudine in combination with PEGASYS/COPEGUS developed severe neutropenia (ANC <500) and severe anemia (hemoglobin <8 g/dL) more frequently than similar patients not receiving zidovudine (neutropenia 15% vs. 9%) (anemia 5% vs. 1%).

Lamivudine, Stavudine, and Zidovudine

In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogs such as lamivudine, stavudine, and zidovudine. No evidence of a pharmacokinetic or pharmacodynamic interaction was seen when ribavirin was co-administered with lamivudine, stavudine, and/or zidovudine in HIV/HCV coinfected patients (see CLINICAL PHARMACOLOGY: Drug Interactions).

OVERDOSAGE

No cases of overdose with COPEGUS have been reported in clinical trials. Hypocalcemia and hypomagnesemia have been observed in persons administered greater than the recommended dosage of ribavirin. In most of these cases, ribavirin was administered intravenously at dosages up to and in some cases exceeding four times the recommended maximum oral daily dose.

CONTRAINDICATIONS

COPEGUS (ribavirin) is contraindicated in:

• Patients with known hypersensitivity to COPEGUS or to any component of the tablet.
• Women who are pregnant.
• Men whose female partners are pregnant.
• Patients with hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia).

COPEGUS and PEGASYS combination therapy is contraindicated in patients with:

• Autoimmune hepatitis.
• Hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment.
• Hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment.