Drug Interactions between edoxaban and pemigatinib

Pemigatinib may be taken with or without food. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with pemigatinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of pemigatinib. This may increase the frequency and severity of serious side effects such as elevated phosphate levels in the blood (which can eventually lead to low blood calcium levels; calcium deposits in the skin, muscles, and other tissues; anemia; muscle cramps; seizures; and irregular heart rhythm), eye and vision problems, joint pain, mouth sores and inflammation, hair loss, diarrhea, nausea, vomiting, and constipation. Talk to your doctor if you have any questions or concerns. 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 factor Xa inhibitors is contraindicated in patients with active pathological bleeding as these agents increase the risk of bleeding and can cause serious or fatal hemorrhages. Caution is recommended when prescribing factor Xa inhibitors to patients at increased risk of bleeding, including patients undergoing procedures where bleeding may cause serious complications. Such patients include those undergoing spinal/epidural anesthesia or spinal puncture; these patients are at high risk of an epidural or spinal hematoma, which can result in long-term or permanent paralysis. In general, when using factor Xa inhibitors, the risk of thrombotic events should be weighed against the risk of bleeding.

Direct acting oral anticoagulants including factor Xa inhibitors and some thrombin inhibitors as dabigatran, are not recommended for use in patients with antiphospholipid syndrome (APS). Treatment with these drugs has been associated with increased rates of recurrent thrombotic events, especially in patients with triple positive APS.

The use of factor Xa inhibitors (including apixaban and edoxaban) is not recommended in patients with moderate or severe liver dysfunction (Child-Pugh B or C) as these patients may have intrinsic coagulation abnormalities.

The recommended dosage of pemigatinib should be reduced in patients with severe hepatic dysfunction. No dose adjustment is recommended for patients with mild or moderate hepatic impairment.

The use of some factor Xa inhibitors (including apixaban, edoxaban, and rivaroxaban) is not recommended in patients with prosthetic heart valves; safety and efficacy have not been established in such patients.

The use of some factor Xa inhibitors (including apixaban, edoxaban, and rivaroxaban) is not recommended in patients with prosthetic heart valves; safety and efficacy have not been established in such patients.

Edoxaban is eliminated primarily as unchanged drug in the urine. Blood levels of edoxaban are increased in patients with renal dysfunction. The use of edoxaban is not recommended in patients with CrCl < 15 mL/min. It is recommended to reduce the dose to 30 mg once daily in these patients. The clearance of edoxaban is not significantly affected by hemodialysis. Care should be exercised when using this agent in patients with renal dysfunction.

The recommended dosage of pemigatinib should be reduced in patients with severe renal disease. No dose adjustment is recommended for patients with mild or moderate renal impairment, or those patients with end-stage renal disease receiving intermittent hemodialysis.

Pemigatinib can cause retinal pigment epithelial detachment (RPED), which may cause symptoms such as blurred vision, visual floaters, or photopsia. A comprehensive ophthalmological examination including an optical coherence tomography should be performed prior to treatment initiation. Patients with visual disturbances should be closely monitored.