Drug Interactions between peginterferon alfa-2a and Tyzeka

CONTRAINDICATED: The risk and severity of peripheral neuropathy may be increased during coadministration of telbivudine with alfa interferons. The mechanism of interaction has not been described, although these agents individually have been associated with neuropathy and may have additive effects during concomitant use. A pharmacokinetic interaction may also be involved. Peripheral neuropathy has been reported as an adverse event in 0.3% (5/2000) of subjects receiving telbivudine monotherapy in clinical trials and also rarely in postmarketing reports. By contrast, peripheral neuropathy was reported as a serious event in 10% of patients who participated in a pilot clinical trial investigating the combination of telbivudine 600 mg daily with pegylated interferon alfa-2a 180 mcg once weekly by subcutaneous administration. Non-serious cases of peripheral neuropathy were also reported. Symptoms included weakness and paresthesias and pain in the legs, with the time to onset being 3 months in most cases. A similar risk cannot be excluded for combination treatment with other dosage regimens of pegylated interferon alfa-2a or with other alfa interferons, whether pegylated or standard. Pharmacokinetically, there appears to be no statistically significant effect of a single 180 subcutaneous dose of peginterferon alfa-2a (180 micrograms) on the steady-state plasma concentrations of telbivudine. Conversely, mean peginterferon alfa-2a peak plasma concentration (Cmax) and systemic exposure (AUC) were increased by approximately 64% and 40%, respectively, when coadministered with multiple doses of telbivudine 600 mg in healthy subjects. However, no definitive conclusion could be drawn regarding the effects of telbivudine on the pharmacokinetics of peginterferon alfa-2a due to the high interindividual variability in plasma levels of the latter.

MANAGEMENT: The safety and efficacy of telbivudine in combination with alfa interferons for the treatment of chronic hepatitis B have not been demonstrated, thus concomitant use should generally be avoided. Coadministration of telbivudine with pegylated interferon alfa-2a is specifically contraindicated by the manufacturer. Patients treated with these agents should be advised to report any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without gait disturbance. Telbivudine therapy should be interrupted if peripheral neuropathy is suspected, and discontinued if confirmed.

Switch to consumer interaction data