Drug Interactions between abemaciclib and fluconazole

Grapefruit juice can increase the blood levels of abemaciclib. This may increase side effects such as nausea, vomiting, diarrhea, abdominal pain, decreased appetite, mouth sores, blood clots, hair loss, liver problems, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. You should avoid the consumption of grapefruit and grapefruit juice during treatment with abemaciclib. Be sure to take the medication at approximately the same time everyday to maintain consistent blood levels and effects. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

The dosing frequency of abemaciclib should be reduced to once daily when it is administered to patients with severe hepatic impairment (Child-Pugh C). No dosage adjustments are necessary for patients with mild or moderate hepatic impairment (Child-Pugh A or B). Hepatotoxicity has been reported with the use of abemaciclib. It is recommended to monitor liver function tests prior to the start of therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation.

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.

Diarrhea, sometimes associated with dehydration and infection, has occurred in patients receiving abemaciclib. Diarrhea incidence was greatest during the first month of abemaciclib dosing. Care should be exercised when treating patients with symptoms of diarrhea. Treatment discontinuation may be required for Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization. Resume treatment at the next lower dose once toxicity resolves to <= Grade 1 diarrhea.

Diarrhea, sometimes associated with dehydration and infection, has occurred in patients receiving abemaciclib. Diarrhea incidence was greatest during the first month of abemaciclib dosing. Care should be exercised when treating patients with symptoms of diarrhea. Treatment discontinuation may be required for Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization. Resume treatment at the next lower dose once toxicity resolves to <= Grade 1 diarrhea.

Neutropenia, including febrile neutropenia has occurred in patients receiving abemaciclib. Care should be exercised when prescribing this agent to patients with preexisting neutropenia. It is recommended to monitor complete blood counts prior to the start of therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

Diarrhea, sometimes associated with dehydration and infection, has occurred in patients receiving abemaciclib. Diarrhea incidence was greatest during the first month of abemaciclib dosing. Care should be exercised when treating patients with symptoms of diarrhea. Treatment discontinuation may be required for Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization. Resume treatment at the next lower dose once toxicity resolves to <= Grade 1 diarrhea.

Patients treated with abemaciclib have reported severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis. It is recommended to monitor patients for pulmonary symptoms indicative of ILD/pneumonitis such as, hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Dose interruption or dose reduction is recommended for patients who develop persistent or recurrent Grade 2 ILD/pneumonitis. Permanently discontinue therapy in all patients with Grade 3 or 4 ILD or pneumonitis.

Neutropenia, including febrile neutropenia has occurred in patients receiving abemaciclib. Care should be exercised when prescribing this agent to patients with preexisting neutropenia. It is recommended to monitor complete blood counts prior to the start of therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Venous thromboembolic events have been reported with the use of abemaciclib. Care should be exercised when using this agent in patients with risk factors or history of venous thromboembolic events. It is recommended to monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.