Interactions between Paclitaxel and Vfend

PACLitaxel has a moderate potential interaction with Anaphylaxis.

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in patients receiving paclitaxel. It is recommended that all patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists. Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel injection.

PACLitaxel has a major potential interaction with Arrhythmia.

Severe conduction abnormalities, some requiring pacemaker placement, have been reported during paclitaxel therapy. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to conduction disorders. Clinical monitoring of cardiac function is recommended during subsequent paclitaxel therapy.

The voriconazole in Vfend has a moderate potential interaction with Arrhythmia.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

PACLitaxel has a major potential interaction with Bleeding Disorder.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

PACLitaxel has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

The voriconazole in Vfend has a moderate potential interaction with Bone Marrow Transplantation.

Patients with risk factors for acute pancreatitis (e.g., recent chemotherapy, hematopoietic stem cell transplantation) should be monitored for the development of pancreatitis during voriconazole therapy.

The voriconazole in Vfend has a moderate potential interaction with Cardiomyopathy.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

The voriconazole in Vfend has a moderate potential interaction with Electrolyte Abnormalities.

Electrolyte disturbances (such as hypokalemia, hypomagnesemia, and hypocalcemia) should be monitored and corrected before and during voriconazole therapy.

PACLitaxel has a major potential interaction with Fever.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

The voriconazole in Vfend has a moderate potential interaction with Galactosemia.

Voriconazole tablets contain lactose and should not be given to patients with galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption. Voriconazole oral suspension contains sucrose.

PACLitaxel has a major potential interaction with Infection.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

The voriconazole in Vfend has a moderate potential interaction with Lactose Intolerance.

Voriconazole tablets contain lactose and should not be given to patients with galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption. Voriconazole oral suspension contains sucrose.

PACLitaxel has a major potential interaction with Liver Disease.

Paclitaxel is extensively metabolized by the liver. Patients with moderate to severe hepatic impairment may be at increased risk for hepatotoxicity. Additionally, myelotoxicity of paclitaxel may be exacerbated in patients with serum total bilirubin >2 times ULN. Therapy with paclitaxel should be administered cautiously and at a reduced dosage in patients with compromised hepatic function.

The voriconazole in Vfend has a moderate potential interaction with Liver Disease.

Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure [including fatalities]) have been reported infrequently during voriconazole therapy. Hepatic reactions have primarily occurred in patients with serious underlying medical conditions (mainly hematological malignancy). Serum transaminase levels and bilirubin should be measured at the start of and during voriconazole therapy, according to the manufacturer product information.

Voriconazole is primarily metabolized by the liver and has been shown to accumulate significantly in patients with impaired hepatic function. Adult patients with baseline liver function tests (ALT, AST) of up to 5 times the upper limit of normal do not require dose adjustments; however, liver function tests should continue to be monitored for further elevations. The manufacturer recommends that the maintenance dose be halved in adult patients with mild to moderate liver dysfunction/cirrhosis (Child-Pugh A and B). Voriconazole has not been studied in adult patients with severe liver dysfunction/cirrhosis (Child-Pugh C) or in patients with chronic hepatitis B or C; no dosing recommendations are available for patients with severe liver dysfunction. Voriconazole should only be used in patients with severe liver dysfunction if the benefit outweighs the potential risk. Patients with liver dysfunction must be carefully monitored for drug toxicity. Dosage adjustment has not been established in pediatric patients with liver dysfunction.

The voriconazole in Vfend has a moderate potential interaction with Myeloproliferative Disorders.

Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure [including fatalities]) have been reported infrequently during voriconazole therapy. Hepatic reactions have primarily occurred in patients with serious underlying medical conditions (mainly hematological malignancy). Serum transaminase levels and bilirubin should be measured at the start of and during voriconazole therapy, according to the manufacturer product information.

Voriconazole is primarily metabolized by the liver and has been shown to accumulate significantly in patients with impaired hepatic function. Adult patients with baseline liver function tests (ALT, AST) of up to 5 times the upper limit of normal do not require dose adjustments; however, liver function tests should continue to be monitored for further elevations. The manufacturer recommends that the maintenance dose be halved in adult patients with mild to moderate liver dysfunction/cirrhosis (Child-Pugh A and B). Voriconazole has not been studied in adult patients with severe liver dysfunction/cirrhosis (Child-Pugh C) or in patients with chronic hepatitis B or C; no dosing recommendations are available for patients with severe liver dysfunction. Voriconazole should only be used in patients with severe liver dysfunction if the benefit outweighs the potential risk. Patients with liver dysfunction must be carefully monitored for drug toxicity. Dosage adjustment has not been established in pediatric patients with liver dysfunction.

PACLitaxel has a major potential interaction with Peripheral Neuropathy.

Dose-dependent peripheral neuropathy has been reported in 60% of patients during paclitaxel therapy. Severe peripheral neuropathy is rare and requires a 20% reduction in dosage of paclitaxel. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to peripheral neuropathy.

The voriconazole in Vfend has a moderate potential interaction with Renal Dysfunction.

The pharmacokinetics of voriconazole are not significantly altered by impaired renal function. However, accumulation of the IV vehicle, sulfobutyl ether beta-cyclodextrin sodium (SBECD), occurs in patients with moderate or severe renal dysfunction (CrCl less than 50 mL/min). The mean systemic exposure (AUC) and Cmax of SBECD were increased 4-fold and almost 50%, respectively, in moderately impaired patients compared to controls with normal renal function. The manufacturer recommends that oral voriconazole be used in patients with moderate to severe renal dysfunction, unless after assessing the benefit/risk to the patient, use of IV voriconazole is justified; serum creatinine levels should be monitored closely in these patients, and if increases occur, switching to oral voriconazole should be considered. No dosage adjustment is necessary when using oral voriconazole. Monitoring of renal function (including laboratory evaluation of serum creatinine) is recommended. Dosage adjustment has not been established in pediatric patients with renal dysfunction.