Drug Interactions between sorafenib and thalidomide

MONITOR: Thalidomide can cause peripheral neuropathy, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Peripheral neuropathy is a common, potentially severe side effect of thalidomide that may be irreversible. The condition generally occurs following chronic use over a period of months, although there have also been reported cases following relatively short-term use. The median time to first neuropathy event was 42.3 weeks in one phase 3 study. Occasionally, symptoms may occur some time after thalidomide treatment has been discontinued. The incidence of neuropathy requiring thalidomide discontinuation, dosage reduction, or interruption increases with cumulative dose and duration of therapy.

MANAGEMENT: Caution is advised if thalidomide is used in combination with other neurotoxic agents. All patients treated with thalidomide should be examined at monthly intervals for the first three months of therapy and periodically thereafter to detect early signs of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Electrophysiological testing may be performed at baseline and every six months during therapy to detect asymptomatic neuropathy. Consideration should be given to immediate discontinuation of thalidomide in patients who develop peripheral neuropathy to limit further damage. Symptoms may improve or return to baseline in some patients upon discontinuation of thalidomide, although the complete time course of this toxicity has not been fully characterized. If necessary, therapy should generally be reinstituted only after neuropathy returns to baseline status. A dosage reduction of thalidomide may be required as clinically indicated.

MONITOR: Thalidomide can cause bradycardia and may potentiate the risk of torsade de pointes arrhythmia associated with the use of drugs that prolong the QT interval. Cases of bradycardia have been associated with thalidomide use, some requiring medical interventions. The clinical significance and underlying aetiology of the bradycardia observed with thalidomide treatment have not been established.

MANAGEMENT: Because bradycardia is a risk factor for torsade de pointes arrhythmia, caution is advised when thalidomide is used with drugs that can prolong the QT interval or induce torsade de pointes arrhythmia. Patients should be monitored for bradycardia, atrioventricular block and syncope, and advised to seek medical attention if they experience dizziness, lightheadedness, fainting, shortness of breath, or slow or irregular heartbeat. A dose reduction of thalidomide or discontinuation may be required.