Drug Interactions between Abilify and AccessPak for HIV PEP Expanded with Kaletra

MONITOR: Coadministration with ritonavir, with or without lopinavir, has been suggested in postmarketing reports to increase the proximal tubular intracellular concentrations of tenofovir and potentiate the risk of tenofovir-induced nephrotoxicity. The proposed mechanism is ritonavir inhibition of tenofovir renal tubular secretion into the urine via multidrug resistance protein MRP2. Analysis of data from a compassionate access study in which 271 patients with advanced HIV disease received the combination for a mean duration of 63 weeks revealed no clinically significant nephrotoxicity associated with coadministration. However, there have been case reports of renal failure associated with acute tubular necrosis, Fanconi's syndrome, and nephrogenic diabetes insipidus in patients treated with tenofovir disoproxil fumarate in combination with ritonavir. Some patients had incomplete recovery of renal function more than a year after cessation of tenofovir therapy. Ritonavir given in combination with lopinavir has also been reported to modestly increase the plasma concentrations of tenofovir. In contrast, both slight decreases and no change in lopinavir and ritonavir concentrations have been reported.

MANAGEMENT: Caution is advised if tenofovir disoproxil fumarate is prescribed with ritonavir. Renal function should be monitored regularly, including surveillance for signs of tubulopathy such as glycosuria, acidosis, increases in serum creatinine level, electrolyte disturbances (e.g., hypokalemia, hypophosphatemia), and proteinuria. The same precaution may be applicable during therapy with other protease inhibitors based on their similar pharmacokinetic profile, although clinical data are lacking. Nelfinavir reportedly does not alter the pharmacokinetics of tenofovir, or vice versa. Tenofovir administration should be discontinued promptly if nephropathy develops.

Switch to consumer interaction data

ADJUST DOSE: Coadministration with ketoconazole or other potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of aripiprazole, which is partially metabolized by the isoenzyme. According to the product labeling, administration of aripiprazole (15 mg single dose) following pretreatment with ketoconazole (200 mg/day for 14 days) increased the systemic exposure (AUC) to aripiprazole and its active metabolite, dehydro-aripiprazole, by 63% and 77%, respectively, compared to administration of aripiprazole alone. The effect of a higher dosage of ketoconazole has not been studied.

MANAGEMENT: Pharmacologic response to aripiprazole should be monitored more closely whenever ketoconazole or other potent inhibitors of CYP450 3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, ketolide and certain macrolide antibiotics) are added to or withdrawn from therapy. The manufacturer recommends that aripiprazole dosage be reduced to one-half the normal dosage during concomitant administration with ketoconazole, and additional dosage adjustments be made based on clinical evaluation. Although clinical data are lacking, similar dosage adjustments may be appropriate during coadministration with other potent CYP450 3A4 inhibitors. Aripiprazole dosage should be increased accordingly if these agents are discontinued.

Switch to consumer interaction data

MONITOR: Coadministration with ritonavir, with or without lopinavir, has been suggested in postmarketing reports to increase the proximal tubular intracellular concentrations of tenofovir and potentiate the risk of tenofovir-induced nephrotoxicity. The proposed mechanism is ritonavir inhibition of tenofovir renal tubular secretion into the urine via multidrug resistance protein MRP2. Analysis of data from a compassionate access study in which 271 patients with advanced HIV disease received the combination for a mean duration of 63 weeks revealed no clinically significant nephrotoxicity associated with coadministration. However, there have been case reports of renal failure associated with acute tubular necrosis, Fanconi's syndrome, and nephrogenic diabetes insipidus in patients treated with tenofovir disoproxil fumarate in combination with ritonavir. Some patients had incomplete recovery of renal function more than a year after cessation of tenofovir therapy. Ritonavir given in combination with lopinavir has also been reported to modestly increase the plasma concentrations of tenofovir. In contrast, both slight decreases and no change in lopinavir and ritonavir concentrations have been reported.

MANAGEMENT: Caution is advised if tenofovir disoproxil fumarate is prescribed with ritonavir. Renal function should be monitored regularly, including surveillance for signs of tubulopathy such as glycosuria, acidosis, increases in serum creatinine level, electrolyte disturbances (e.g., hypokalemia, hypophosphatemia), and proteinuria. The same precaution may be applicable during therapy with other protease inhibitors based on their similar pharmacokinetic profile, although clinical data are lacking. Nelfinavir reportedly does not alter the pharmacokinetics of tenofovir, or vice versa. Tenofovir administration should be discontinued promptly if nephropathy develops.

Switch to consumer interaction data

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.

Switch to consumer interaction data