BOSULIF® (bosutinib) 2 DOSAGE AND ADMINISTRATION

(bosutinib)

Prescribing Information

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage is taken orally once daily with food. Swallow tablets whole. Do not cut, crush, break or chew tablets. Continue treatment with BOSULIF until disease progression or intolerance to therapy.

Capsules may be swallowed whole. For patients who are unable to swallow a whole capsule(s), each capsule can be opened and the contents mixed with applesauce or yogurt. Mixing the capsule contents with applesauce or yogurt cannot be considered a substitute of a proper meal.

If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day.

Dosage in Adult Patients with Newly-Diagnosed CP Ph+ CML

The recommended dosage of BOSULIF is 400 mg orally once daily with food.

Dosage in Adult Patients with CP, AP, or BP Ph+ CML with Resistance or Intolerance to Prior Therapy

The recommended dosage of BOSULIF is 500 mg orally once daily with food.

Dosage in Pediatric Patients with Newly-Diagnosed CP Ph+ CML or with CP Ph+ CML with Resistance or Intolerance to Prior Therapy

The recommended dose of BOSULIF for pediatric patients with newly-diagnosed CP Ph+ CML is 300 mg/m2 orally once daily with food and the recommended dosage for pediatric patients with CP Ph+ CML that is resistant or intolerant to prior therapy is 400 mg/m2 orally once daily with food and dose recommendations are provided in Table 1. As appropriate, the desired dose can be attained by combining different strengths of BOSULIF tablets or capsules.

Table 1: Dosing of BOSULIF for Pediatric Patients with Newly-Diagnosed CP Ph+ CML or with CP Ph+ CML with Resistance or Intolerance to Prior Therapy
* BSA=Body Surface Area † maximum starting dose (corresponding to maximum starting dose in adult indication)
BSA*	Newly-Diagnosed Recommended Dose (Once Daily)	Resistant or Intolerant Recommended Dose (Once Daily)
< 0.55 m2	150 mg	200 mg
0.55 to < 0.63 m2	200 mg	250 mg
0.63 to < 0.75 m2	200 mg	300 mg
0.75 to < 0.9 m2	250 mg	350 mg
0.9 to < 1.1 m2	300 mg	400 mg
≥ 1.1 m2	400 mg†	500 mg†

Preparation Instructions for BOSULIF Capsules Mixed with Applesauce or Yogurt

For patients who are unable to swallow capsules, the contents of the capsules can be mixed with applesauce or yogurt. Remove the required number of capsules from the container to prepare the dose as instructed and the amount of either room temperature applesauce or yogurt in a clean container. Carefully open each capsule, add the entire capsule content of each capsule into the applesauce or yogurt, then mix the entire dose into the applesauce or yogurt. Patients should immediately consume the full mixture in its entirety, without chewing. Do not store the mixture for later use. If the entire preparation is not swallowed do not take an additional dose. Wait until the next day to resume dosing.

Table 2: BOSULIF Dose Using Capsules and Soft Food Volumes
Dose	Volume of Applesauce or Yogurt
100 mg	10 mL (2 teaspoons)
150 mg	15 mL (3 teaspoons)
200 mg	20 mL (4 teaspoons)
250 mg	25 mL (5 teaspoons)
300 mg	30 mL (6 teaspoons)
350 mg	30 mL (6 teaspoons)
400 mg	35 mL (7 teaspoons)
450 mg	40 mL (8 teaspoons)
500 mg	45 mL (9 teaspoons)
550 mg	45 mL (9 teaspoons)
600 mg	50 mL (10 teaspoons)

2.2 Dose Escalation

In clinical studies of adult patients with Ph+ CML, dose escalation by increments of 100 mg once daily to a maximum of 600 mg once daily was allowed in patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and who did not have Grade 3 or higher adverse reactions at the recommended starting dosage.

In pediatric patients with BSA <1.1 m2 and an insufficient response after 3 months consider increasing dose by 50 mg increments up to maximum of 100 mg above starting dose. Dose increases for insufficient response in pediatric patients with BSA ≥1.1 m2 can be conducted similarly to adult recommendations in 100 mg increments.

The maximum dose in pediatric and adult patients is 600 mg once daily.

2.3 Dosage Adjustments for Non-Hematologic Adverse Reactions

Elevated liver transaminases: If elevations in liver transaminases greater than 5×institutional upper limit of normal (ULN) occur, withhold BOSULIF until recovery to less than or equal to 2.5×ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue BOSULIF. If transaminase elevations greater than or equal to 3×ULN occur concurrently with bilirubin elevations greater than 2×ULN and alkaline phosphatase less than 2×ULN (Hy's law case definition), discontinue BOSULIF [see Warnings and Precautions (5.3)].

Diarrhea: For National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3–4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment), withhold BOSULIF until recovery to Grade less than or equal to 1. BOSULIF may be resumed at 400 mg once daily [see Warnings and Precautions (5.1)].

For other clinically significant, moderate or severe non-hematological toxicity, withhold BOSULIF until the toxicity has resolved, then consider resuming BOSULIF at a dose reduced by 100 mg taken once daily. If clinically appropriate, consider re-escalating the dose of BOSULIF to the starting dose taken once daily.

In pediatric patients, dose adjustments for non-hematologic toxicities can be conducted similarly to adults, however the dose reduction increments may differ. For pediatric patients with BSA <1.1 m2, reduce dose by 50 mg initially followed by additional 50 mg increment if the adverse reaction (AR) persists. For pediatric patients with BSA ≥1.1 m2 or greater, reduce dose similarly to adults.

2.4 Dosage Adjustments for Myelosuppression

Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 3).

Table 3: Dose Adjustments for Neutropenia and Thrombocytopenia in Adult and Pediatric Patients
* Absolute Neutrophil Count
ANC* less than 1000×106/L or Platelets less than 50,000×106/L	Withhold BOSULIF until ANC greater than or equal to1000×106/L and platelets greater than or equal to 50,000×106/L. Resume treatment with BOSULIF at the same dose if recovery occurs within 2 weeks. If blood counts remain low for greater than 2 weeks, upon recovery, reduce dose by 100 mg and resume treatment, or by 50 mg in pediatric patients with BSA <1.1 m2 and resume treatment. If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment, or by an additional 50 mg in pediatric patients with BSA <1.1 m2 and resume treatment.

2.5 Dosage Adjustments for Renal Impairment or Hepatic Impairment

The recommended starting doses for patients with renal and hepatic impairment are described in Table 4 below.

Table 4: Dose Adjustments for Renal and Hepatic Impairment in Adult Patients
		Recommended Starting Dosage
[see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)].
		Newly-diagnosed chronic phase Ph+ CML	Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy
Normal renal and hepatic function		400 mg daily	500 mg daily
Renal impairment
	Creatinine clearance 30 to 50 mL/min	300 mg daily	400 mg daily
	Creatinine clearance less than 30 mL/min	200 mg daily	300 mg daily
Hepatic impairment
	Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C)	200 mg daily	200 mg daily

Table 5: Dosage Adjustments for Renal and Hepatic Impairment in Pediatric Patients
[see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)].
* BSA=Body Surface Area
	Newly-Diagnosed CP Ph+ CML Recommended Starting Dose (Once Daily) By Organ Function
Pediatric Patients by Separated BSA* Band	Normal renal and hepatic function	Renal Impairment: Creatinine clearance 30 to 50 mL/min	Renal Impairment: Creatinine clearance less than 30 mL/min	Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C)
Pediatric < 0.55 m2	150 mg	100 mg	100 mg	100 mg
Pediatric 0.55 to < 0.63 m2	200 mg	150 mg	100 mg	100 mg
Pediatric 0.63 to < 0.75 m2	200 mg	150 mg	100 mg	100 mg
Pediatric 0.75 to < 0.9 m2	250 mg	200 mg	150 mg	100 mg
Pediatric 0.9 to < 1.1 m2	300 mg	200 mg	200 mg	150 mg
Pediatric ≥ 1.1 m2	400 mg	300 mg	200 mg	200 mg
	CP Ph+ CML with Resistance or Intolerance to Prior Therapy Recommended Starting Dose (Once Daily) By Organ Function
Pediatric Patients by Separated BSA* Band	Normal renal and hepatic function	Renal Impairment: Creatinine clearance 30 to 50 mL/min	Renal Impairment: Creatinine clearance less than 30 mL/min	Hepatic Impairment: Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C)
Pediatric < 0.55 m2	200 mg	150 mg	100 mg	100 mg
Pediatric 0.55 to < 0.63 m2	250 mg	200 mg	150 mg	100 mg
Pediatric 0.63 to < 0.75 m2	300 mg	200 mg	200 mg	150 mg
Pediatric 0.75 to < 0.9 m2	350 mg	250 mg	200 mg	150 mg
Pediatric 0.9 to < 1.1 m2	400 mg	300 mg	250 mg	200 mg
Pediatric ≥ 1.1 m2	500 mg	400 mg	300 mg	200 mg

Medication Guide

MEDICATION GUIDE

PATIENT INFORMATION
BOSULIF® (BAH-su-lif) (bosutinib) tablets		BOSULIF® (BAH-su-lif) (bosutinib) capsules
What is BOSULIF? BOSULIF is a prescription medicine used to treat: • adults and children 1 year of age and older who have a certain type of leukemia called chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) who are newly-diagnosed or who no longer benefit from or did not tolerate other treatment. • adults with accelerated phase (AP), or blast phase (BP) Ph+ CML who can no longer benefit from or did not tolerate other treatment. It is not known if BOSULIF is safe and effective in children less than 1 year of age with CP Ph+ CML who are newly‑diagnosed or who no longer benefit from or did not tolerate other treatment or in children with AP Ph+ CML or BP Ph+ CML.
Do not take BOSULIF if you are allergic to bosutinib or any of the ingredients in BOSULIF. See the end of this leaflet for a complete list of ingredients of BOSULIF.
Before taking BOSULIF, tell your doctor about all of your medical conditions, including if you: • have liver problems • have heart problems • have kidney problems • have high blood pressure • have diabetes • are pregnant or plan to become pregnant. BOSULIF can harm your unborn baby. Females who are able to become pregnant should have a pregnancy test before starting treatment with BOSULIF. Tell your doctor right away if you become pregnant during treatment with BOSULIF. o Females who are able to become pregnant should use effective birth control (contraception) during treatment with BOSULIF and for 2 weeks after the last dose. Talk to your doctor about birth control methods that may be right for you. • are breastfeeding or plan to breastfeed. It is not known if BOSULIF passes into your breast milk or if it can harm your baby. Do not breastfeed during treatment with BOSULIF and for 2 weeks after the last dose. Tell your doctor about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. When taken together, BOSULIF and certain other medicines can affect each other. Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.
How should I take BOSULIF? • Take BOSULIF exactly as prescribed by your doctor. • Do not change your dose or stop taking BOSULIF without first talking with your doctor. • If your child takes BOSULIF, your healthcare provider will change the dose as your child grows. • Take BOSULIF with food. • Swallow BOSULIF tablets whole. Do not crush, break, chew or cut BOSULIF tablets. Do not touch or handle crushed or broken BOSULIF tablets. • Swallow BOSULIF capsules whole. If you cannot swallow BOSULIF capsules whole, tell your healthcare provider. • If you cannot swallow BOSULIF capsules whole, see the “Instructions for Use” for detailed instructions on how to prepare and give a dose of BOSULIF capsules by opening the capsules and mixing the capsule contents with applesauce or yogurt. • If you take an antacid or H2 blocker medicine, take it at least 2 hours before or 2 hours after BOSULIF. If you take a Proton Pump Inhibitor (PPI) medicine, talk to your doctor or pharmacist. • You should avoid grapefruit, grapefruit juice, and supplements that contain grapefruit extract during treatment with BOSULIF. Grapefruit products increase the amount of BOSULIF in your body. • If you miss a dose of BOSULIF, take it as soon as you remember. If you miss a dose by more than 12 hours, skip that dose and take your next dose at your regular time. Do not take 2 doses at the same time. • If you take too much BOSULIF, call your doctor or go to the nearest hospital emergency room right away.
What are the possible side effects of BOSULIF? BOSULIF may cause serious side effects, including: • Stomach problems. BOSULIF may cause stomach (abdomen) pain, nausea, diarrhea, vomiting, or blood in your stools. Get medical help right away for any stomach problems. • Low blood cell counts. BOSULIF may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia) and low white blood cell counts (neutropenia). Your doctor should do blood tests to check your blood cell counts regularly during your treatment with BOSULIF. Call your doctor right away if you have unexpected bleeding or bruising, blood in your urine or stools, fever, or any signs of an infection. • Liver problems. Your doctor should do blood tests to check your liver function regularly during your treatment with BOSULIF. Call your doctor right away if your skin or the white part of your eyes turns yellow (jaundice) or you have dark "tea color" urine. • Heart problems. BOSULIF may cause heart problems, including heart failure and decreased blood flow to the heart which can lead to heart attack. Get medical help right away if you get shortness of breath, weight gain, chest pain, or swelling in your hands, ankles or feet. • Your body may hold too much fluid (fluid retention). Fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Get medical help right away if you get any of the following symptoms during your treatment with BOSULIF:
	o shortness of breath and cough o chest pain o swelling in your hands, ankles, or feet	o swelling all over your body o weight gain
• Kidney problems. Your doctor should do tests to check your kidney function when you start treatment with BOSULIF and during your treatment. Call your doctor right away if you get any of the following symptoms during your treatment with BOSULIF: o you urinate more often than normal o you urinate less often than normal o you make a much larger amount of urine than normal o you make a much smaller amount of urine than normal The most common side effects of BOSULIF in adults and children with CML include:
• diarrhea • stomach (abdominal) pain • vomiting • nausea • rash • tiredness • liver problems		• headache • fever • decreased appetite • respiratory tract infections (infections in nose, throat or lungs) • constipation • changes in certain blood tests. Your doctor may do blood tests during treatment with BOSULIF to check for changes
Tell your doctor or get medical help right away if you get respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, rash or itching while taking BOSULIF. These may be symptoms of a severe allergic reaction. Your doctor may change your dose, temporarily stop, or permanently stop treatment with BOSULIF if you have certain side effects. BOSULIF may cause fertility problems in females and males. This may affect your ability to have a child. Talk to your doctor if this is a concern for you. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BOSULIF. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store BOSULIF? • Store BOSULIF tablets and capsules at room temperature between 68°F to 77°F (20°C to 25°C). • The BOSULIF tablets and capsules bottle has a child-resistant closure. • The BOSULIF tablets bottle contains a desiccant to help keep your medicine dry (protect it from moisture). Keep the desiccant in the bottle. Do not eat the desiccant. • Store the BOSULIF capsules in the original bottle. • Ask your doctor or pharmacist about the right way to throw away outdated or unused BOSULIF. Keep BOSULIF and all medicines out of the reach of children.
General information about the safe and effective use of BOSULIF. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use BOSULIF for a condition for which it is not prescribed. Do not give BOSULIF to other people even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about BOSULIF that is written for health professionals.
What are the ingredients in BOSULIF? Active ingredient: bosutinib. Inactive ingredients: Tablets: croscarmellose sodium, iron oxide red (for 400 mg, and 500 mg tablet) and iron oxide yellow (for 100 mg, and 400 mg tablet), magnesium stearate, microcrystalline cellulose, poloxamer, polyethylene glycol, polyvinyl alcohol, povidone, talc and titanium dioxide. Capsules: croscarmellose sodium, gelatin, magnesium stearate, mannitol, microcrystalline cellulose, poloxamer, povidone, red iron oxide, titanium dioxide, yellow iron oxide. The printing ink contains black iron oxide, potassium hydroxide, propylene glycol, shellac, strong ammonia solution. For more information, go to www.Bosulif.com or www.pfizermedicalinformation.com or call 1-800-438-1985.

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised 12/2024

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