Geriatric Patients

The pharmacokinetics of geriatric subjects (> 65 years of age) treated with a single subcutaneous dose of1.0 mg/kg of PEG-Intron were similar in C_max, AUC, clearance, or elimination half-life as compared to younger subjects (28 to 44 years of age).

Effect of Food on Absorption of Ribavirin Both AUC_tf and C_max increased by 70% when REBETOL Capsules wereadministered with a high-fat meal (841 kcal, 53.8 g fat, 31.6 g protein, and 57.4 g carbohydrate) in a single-dose pharmacokinetic study. (See DOSAGE AND ADMINISTRATION.)

The pharmacokinetics of representative drugs metabolized by CYP1A2 (caffeine), CYP2C8/9 (tolbutamide), CYP2D6 (dextromethorphan), CYP3A4 (midazolam) and N-acetyltransferase (dapsone) were studied in 22 patients with chronic hepatitis C who received PEG-Intron (1.5mcg/kg) once weekly for 4 weeks. PEG-Intron treatment resulted in a 28% (mean) increase in a measure of CYP2C8/9 activity. PEG-Intron treatment also resulted in a 66% (mean) increase in a measure of CYP2D6 activity; however, the effect was variable as 13 patients had an increase, 5 patients had a decrease, and 4 patients had no significant change (see PRECAUTIONS: Drug Interactions).

No significant effect was observed on the pharmacokinetics of representatives drugs metabolized by CYP1A2, CYP3A4, or N-acetyltransferase. The effects of PEG-Intron on CYP2C19 activity were not assessed.

The pharmacokinetics of concomitant administration of methadone and PEG-Intron were evaluated in 18 PEG-Intron naïve chronic hepatitis C patients receiving 1.5 mg/kg/week PEG-Intron SC weekly. All patients were on stable methadone maintenance therapy receiving ≥ 40 mg/day prior to initiating PEG-Intron. Mean methadone AUC was approximately 16% higher after 4 weeks of PEG-Intron treatment as compared to baseline. In 2 patients, methadone AUC was approximately double after 4 weeks of PEG-Intron treatment as compared to baseline (see PRECAUTIONS: Drug Interactions).

Ribavirin has been shown in vitro to inhibit phosphorylation of zidovudine, lamivudine and stavudine. However, in a study with another pegylated interferon in combination with ribavirin, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n=18) stavudine (n=10) or zidovudine (n=6) were co-administered as part of a multi-drug regimen to HIV./HCV coinfected patients. Exposure to didanosine or its active metabolite (dideoxyadenosine 5†-tirphosphate) is increased when didanosine is co-administered with ribavirin, which could cause or worsen clinical toxicities (See PRECAUTIONS : Drug Interactions).

CLINICAL STUDIES

A randomized study compared treatment with PEG-Intron (0.5, 1.0, or 1.5 mg/kg once weekly SC) to treatment with INTRON A, (3 million units three times weekly SC) in 1219 adults with chronic hepatitis from HCV infection. The patients were not previously treated with interferon alfa, had compensated liver disease, detectable HCV RNA, elevated ALT, and liver histopathology consistent with chronic hepatitis. Patients were treated for 48 weeks and were followed for 24 weeks post-treatment. Seventy percent of all patients were infected with HCV genotype 1, and 74 percent of all patients had high baseline levels of HCV RNA (more than 2 million copies per mL of serum), two factors known to predict poor response to treatment.

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