Drug Interaction Report

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole. Clinical and in vitro data indicate that aripiprazole is extensively metabolized in the liver primarily via three enzymatic pathways (dehydrogenation, hydroxylation, and N-dealkylation) mediated by CYP450 2D6 and 3A4. When aripiprazole 30 mg once daily was coadministered with the potent CYP450 3A4 inducer carbamazepine at 200 mg twice daily in schizophrenic patients, mean aripiprazole peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 68% and 73%, respectively, compared to administration of aripiprazole alone. Likewise, mean Cmax and AUC of dehydro-aripiprazole were decreased by 69% and 71%, respectively, in the presence of carbamazepine. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: Pharmacologic response to aripiprazole should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the aripiprazole dosage adjusted as necessary. The prescribing information for individual aripiprazole products should be consulted for specific recommendations regarding concomitant use with CYP450 3A4 inducers.

MONITOR: It is uncertain whether aripiprazole causes clinically significant prolongation of the QT interval. In clinical trials with aripiprazole involving patients with schizophrenia or bipolar mania, the incidence of QT prolongation was comparable to placebo. In postmarketing experience, QT prolongation, sudden death, torsade de pointes, ventricular tachycardia, arrhythmia, and cardiopulmonary arrest have been reported. However, these events were very rare or isolated, and many of the patients had preexisting cardiovascular disease, were on concomitant medications known to prolong the QT interval, had risk factors for QT prolongation, took an overdose of aripiprazole, and/or were morbidly obese. On the contrary, most data available in the medical literature suggest that aripiprazole either has no effect on the QT interval, or it may even cause a slight shortening of the QT interval within the dosage range of 10 to 30 mg/day.

MANAGEMENT: Some authorities recommend caution when aripiprazole is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. 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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.