Drug Interactions between lapatinib and lofexidine

MONITOR: Lofexidine has been associated with asymptomatic prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Many psychotherapeutic and CNS-active agents (e.g., sedating antihistamines, antipsychotics) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration of lofexidine with other agents with hypotensive effects may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution is recommended if lofexidine is used in combination with other drugs that can prolong the QT interval. Periodic monitoring with on-treatment electrocardiograms and serum electrolytes (magnesium, potassium) should be considered. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, if taking drugs that also cause CNS or orthostatic effects (e.g., sedating antihistamines, phenothiazines, and neuroleptics), patients should be made aware of the possibility of additive effects with lofexidine and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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