Drug Interactions between brigatinib 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.

Grapefruit juice can increase the blood levels of brigatinib. This may increase side effects such as nausea, vomiting, diarrhea, high blood pressure, high blood sugar, slow heart rate, visual disturbances, anemia, and infections. You should avoid consuming grapefruit and grapefruit juice during treatment with brigatinib. Seek medical attention if you develop paleness, fatigue, dizziness, fainting, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, or pain and burning during urination. Talk to your healthcare provider if you have any questions or concerns.

Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with the use of brigatinib. It is recommended to monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating this drug. Withhold brigatinib in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). Dose modifications or permanent discontinuation may be necessary.

Following a single dose of 90 mg, unbound brigatinib systemic exposure was 37% higher in subjects with severe hepatic impairment (Child-Pugh C) compared to subjects with normal hepatic function. It is recommended to reduce the dose by approximately 40% (i.e., from 180 mg to 120 mg, 120 mg to 90 mg, or from 90 mg to 60 mg) in these patients. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B).

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.

Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with the use of brigatinib. It is recommended to monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating this drug. Withhold brigatinib in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). Dose modifications or permanent discontinuation may be necessary.

Following a single dose of 90 mg, unbound brigatinib systemic exposure was 86% higher in subjects with severe renal impairment [creatinine clearance (CrCl) 15 to 29 mL/min] compared to subjects with normal renal function. It is recommended to reduce dose by approximately 50% (i.e., from 180 mg to 90 mg, or from 90 mg to 60 mg) in these patients. No dose adjustment is recommended for patients with mild or moderate renal impairment [creatinine clearance (CrCl) 30 to 89 mL/min].

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.

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• brigatinib
• pemigatinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.