Panobinostat Lactate and Vfend

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using panobinostat together with voriconazole can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). In addition, voriconazole can increase the blood levels of panobinostat. You may be more likely to experience other side effects such as nausea; vomiting; diarrhea; loss of appetite; fatigue; swelling in the arms or legs; heart problems (e.G., chest pain, heart failure); liver problems; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems, and infections. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

GENERALLY AVOID: Panobinostat can cause dose-dependent prolongation of the QT interval. 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 a premarketing multiple myeloma trial, QTc prolongation with values between 451 to 480 msec and between 481 to 500 msec occurred in 10.8% and 1.3% of patients receiving panobinostat, respectively. A maximum QTcF increase from baseline of 31 to 60 msec and greater than 60 msec was observed in 14.5% and 0.8% of panobinostat-treated patients, respectively. No episodes of QTcF prolongation exceeding 500 msec were reported with panobinostat given at a dose of 20 mg in combination with bortezomib and dexamethasone in the multiple myeloma trial. Pooled clinical data from over 500 patients treated with panobinostat monotherapy at different dose levels for various indications have shown that the incidence of CTC Grade 3 QTc prolongation (i.e., QTcF >500 msec) was approximately 1% overall and 5% or more at a dose of 60 mg or higher. 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, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of panobinostat, which is partially metabolized by the isoenzyme. In 14 patients with advanced or metastatic solid tumors, administration of a single 20 mg dose of panobinostat on day 4 of multiple once daily dosing of 400 mg ketoconazole, a potent CYP450 3A4 inhibitor, resulted in 1.6- and 1.8-fold increases in mean panobinostat peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of panobinostat alone. Ketoconazole caused a greater than 2-fold increase in Cmax and AUC of panobinostat in a limited number of patients. QTc prolongation >30 ms over baseline occurred in 5 patients during concomitant administration, compared to 4 patients during panobinostat alone and 3 patients during ketoconazole alone. Other ECG abnormalities occurred in 6 patients during concomitant administration and 3 patients during either panobinostat or ketoconazole alone. No significant alteration in time to maximum concentration (Tmax) or half-life of panobinostat was observed.

MANAGEMENT: Concomitant use of panobinostat with potent CYP450 3A4 inhibitors that can also prolong the QT interval including ceritinib, clarithromycin, ketoconazole, posaconazole, saquinavir, telithromycin, and voriconazole should generally be avoided. If coadministration with these agents is required, the manufacturer recommends reducing the dose of panobinostat to 10 mg for the treatment of multiple myeloma, given in combination with bortezomib and dexamethasone. ECG and serum electrolytes, including potassium, magnesium and calcium, should be monitored before starting panobinostat therapy and periodically during treatment as clinically indicated. In the premarketing trial, ECGs were performed at baseline and prior to initiation of each cycle for the first 8 cycles. Panobinostat should not be started if baseline QTc is greater than 450 msec. Likewise, treatment should be interrupted in patients who develop QTc prolongation of 480 msec or greater until recovery to less than or equal to Grade 1, then resumed at a reduced dose. In case of recurrence, therapy should be withheld until recovery to less than or equal to Grade 1, then resumed at a further reduced dose if necessary. Permanently discontinue panobinostat therapy if Grade 3 or 4 QTc prolongation does not resolve. 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.

Panobinostat Lactate

Generic Name: panobinostat

Brand name: Farydak

Synonyms: Panobinostat

What is Panobinostat Lactate?

Vfend

Generic Name: voriconazole

Brand name: Vfend, Vfend

Synonyms: Vfend Injection

What is Vfend?