Bosutinib Sandoz
Tyrosine kinase inhibitor for chronic myeloid leukemia (CML)
Quick Facts About Bosutinib Sandoz
Key Takeaways About Bosutinib Sandoz
- Targeted cancer therapy: Bosutinib specifically blocks the BCR-ABL protein responsible for chronic myeloid leukemia, offering precise treatment with fewer effects on healthy cells
- Take with food: Always take bosutinib with a meal to improve absorption and reduce gastrointestinal side effects, especially diarrhea
- Regular monitoring essential: Blood counts, liver function, and kidney function must be checked regularly throughout treatment
- Diarrhea is the most common side effect: Occurs in over 70% of patients but is usually manageable and tends to improve after the first few weeks
- Do not use in pregnancy: Bosutinib may cause fetal harm; effective contraception is mandatory during treatment and for at least one month after the last dose
What Is Bosutinib Sandoz and What Is It Used For?
Bosutinib Sandoz is a tyrosine kinase inhibitor (TKI) used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adults. It works by inhibiting the BCR-ABL oncoprotein, a fusion protein created by the Philadelphia chromosome translocation that drives the uncontrolled growth of leukemic white blood cells.
Chronic myeloid leukemia is a type of blood cancer that originates in the bone marrow and is characterized by the overproduction of abnormal white blood cells. The hallmark of CML is the Philadelphia chromosome, an abnormal chromosome resulting from a translocation between chromosomes 9 and 22. This genetic rearrangement creates the BCR-ABL fusion gene, which produces a constitutively active tyrosine kinase that drives uncontrolled cell proliferation.
Bosutinib belongs to the class of drugs known as tyrosine kinase inhibitors, which have revolutionized the treatment of CML since the introduction of imatinib in 2001. As a second-generation TKI, bosutinib is a dual Src/ABL kinase inhibitor with potent activity against the BCR-ABL oncoprotein. It demonstrates efficacy against many imatinib-resistant BCR-ABL mutations, with the notable exception of the T315I gatekeeper mutation.
Bosutinib Sandoz is indicated for two primary clinical settings. First, it is approved for the treatment of newly diagnosed chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CP CML) in adult patients. Second, it is used for the treatment of chronic phase, accelerated phase, or blast phase Ph+ CML in adults who have been previously treated with one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.
The drug is manufactured by Sandoz as a generic alternative to the original brand Bosulif. It is available as 100 mg film-coated tablets, which allows for flexible dose adjustments based on individual patient response and tolerability. The recommended starting dose varies depending on whether the patient is treatment-naive or previously treated.
How Does Bosutinib Work?
Bosutinib exerts its therapeutic effect by binding to and inhibiting the BCR-ABL tyrosine kinase. This enzyme is constitutively activated in Ph+ CML cells, driving their uncontrolled proliferation and survival. By blocking BCR-ABL signaling, bosutinib effectively halts the growth of leukemic cells and promotes their death (apoptosis).
In addition to BCR-ABL, bosutinib also inhibits members of the Src family of kinases, which play a role in the signaling pathways downstream of BCR-ABL. This dual inhibition may contribute to bosutinib's efficacy in patients who have developed resistance to other TKIs. However, unlike dasatinib (another dual Src/ABL inhibitor), bosutinib has minimal activity against c-KIT and the platelet-derived growth factor receptor (PDGFR), which may account for its different side effect profile.
Clinical trials have demonstrated that bosutinib can achieve deep molecular responses in a significant proportion of patients. In the pivotal BFORE trial comparing bosutinib to imatinib in newly diagnosed CML patients, bosutinib showed superior rates of major molecular response (MMR) at 12 months, supporting its use as a first-line treatment option.
What Should You Know Before Taking Bosutinib Sandoz?
Before starting Bosutinib Sandoz, your doctor must evaluate your liver and kidney function, check your blood counts, and review all medications you are taking. Bosutinib has significant drug interactions and is contraindicated in pregnancy. Certain pre-existing conditions may require dose adjustments or close monitoring.
Contraindications
Bosutinib Sandoz must not be used in patients with known hypersensitivity to bosutinib or any of the excipients in the tablet formulation. It is also contraindicated in patients with severe hepatic impairment (Child-Pugh class C), as the drug is extensively metabolized by the liver and accumulation could lead to increased toxicity.
Pregnancy is an absolute contraindication. Animal studies have shown that bosutinib can cause embryo-fetal toxicity and is potentially teratogenic. There are no adequate and well-controlled studies in pregnant women, but the mechanism of action and animal data strongly suggest risk to the human fetus. Women of childbearing potential must have a negative pregnancy test before starting treatment.
Warnings and Precautions
Several important warnings and precautions apply to bosutinib treatment. Hepatotoxicity is a significant concern: elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported frequently, typically during the first three months of treatment. Liver function should be monitored monthly for the first three months and then as clinically indicated. Treatment should be withheld for significant transaminase elevations and resumed at a reduced dose if levels return to acceptable ranges.
Diarrhea is the most commonly reported adverse event and can be severe. It typically occurs early in treatment and may respond to standard antidiarrheal medications. Patients should be advised to report persistent diarrhea and to maintain adequate hydration. In clinical trials, the median time to onset of diarrhea was within the first month, and the median duration was approximately 2-3 days per episode.
Myelosuppression, including thrombocytopenia, neutropenia, and anemia, can occur and may be severe. Complete blood counts should be performed weekly during the first month and then monthly thereafter, or as clinically indicated. Dose modifications may be required for grade 3 or 4 hematological toxicity.
Fluid retention, including peripheral edema, pleural effusion, pericardial effusion, and pulmonary edema, has been reported. Patients should be monitored for unexpected rapid weight gain, and appropriate management should be initiated promptly. Cardiac events, including QTc prolongation, have been observed rarely, and electrocardiogram monitoring should be considered in patients with risk factors.
Renal toxicity has been reported with bosutinib use. Serum creatinine levels should be monitored during treatment. Dose reductions may be necessary in patients with pre-existing renal impairment or those who develop renal function deterioration during therapy.
Pregnancy and Breastfeeding
Bosutinib is classified as a drug that must not be used during pregnancy. Based on its mechanism of action and findings from animal reproduction studies, bosutinib can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to use highly effective contraception during treatment and for at least one month following the last dose. Male patients with female partners of childbearing potential should also use effective contraception during treatment and for at least one month after the last dose.
It is not known whether bosutinib or its metabolites are excreted in human breast milk. Given the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment with bosutinib and for at least two weeks after the final dose. The decision to discontinue breastfeeding or to discontinue the drug should take into account the importance of the therapy to the mother.
Data on the effects of bosutinib on human fertility are limited. Animal studies have shown some effects on male and female reproductive organs at exposure levels similar to therapeutic doses. Patients who are concerned about fertility should discuss this with their oncologist before starting treatment.
How Does Bosutinib Sandoz Interact with Other Drugs?
Bosutinib is metabolized primarily by the liver enzyme CYP3A4, making it susceptible to significant drug interactions. Strong CYP3A4 inhibitors can increase bosutinib levels (risking toxicity), while strong CYP3A4 inducers can decrease levels (reducing efficacy). Proton pump inhibitors substantially reduce bosutinib absorption.
Drug interactions are a critical consideration in bosutinib therapy because the drug is extensively metabolized by cytochrome P450 3A4 (CYP3A4). Any medication that significantly affects CYP3A4 activity can alter bosutinib plasma levels, potentially leading to either increased toxicity or reduced therapeutic efficacy. Additionally, bosutinib's absorption is pH-dependent, making it susceptible to interactions with acid-reducing agents.
Patients should inform their healthcare provider about all prescription and over-the-counter medications, herbal supplements, and dietary products they are taking before starting bosutinib. Certain food items, particularly grapefruit and Seville oranges, should be avoided during treatment as they contain CYP3A4 inhibitors that can increase bosutinib levels.
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Ketoconazole, itraconazole | Strong CYP3A4 inhibitors increase bosutinib AUC by up to 8-fold | Avoid concomitant use; if unavoidable, reduce bosutinib dose |
| Ritonavir, cobicistat | Strong CYP3A4 inhibitors significantly increase bosutinib exposure | Avoid concomitant use; consider alternative antiretroviral therapy |
| Rifampicin (rifampin) | Strong CYP3A4 inducer decreases bosutinib AUC by approximately 94% | Avoid concomitant use; efficacy of bosutinib is severely compromised |
| Phenytoin, carbamazepine | Strong CYP3A4 inducers substantially reduce bosutinib levels | Avoid concomitant use; consider alternative antiepileptic agents |
| Proton pump inhibitors (omeprazole, lansoprazole) | Increase gastric pH, reducing bosutinib solubility and absorption | Avoid concomitant use; use short-acting antacids separated by >2 hours if needed |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| H2-receptor antagonists (ranitidine, famotidine) | Moderate gastric pH increase may reduce bosutinib absorption | Separate dosing by at least 2 hours; monitor response |
| Moderate CYP3A4 inhibitors (erythromycin, diltiazem) | May moderately increase bosutinib plasma levels | Use with caution; monitor for increased toxicity |
| Warfarin and other anticoagulants | Potential for altered anticoagulant effect | Monitor INR closely; consider LMWH as alternative |
| St. John's Wort (Hypericum perforatum) | CYP3A4 inducer that may decrease bosutinib levels | Avoid concomitant use |
Grapefruit, grapefruit juice, and Seville (bitter) oranges contain compounds that inhibit CYP3A4 in the gut wall. Consuming these products during bosutinib treatment can increase drug levels and the risk of side effects. Patients should avoid these foods throughout the course of treatment.
What Is the Correct Dosage of Bosutinib Sandoz?
The recommended dose of Bosutinib Sandoz is 400 mg once daily with food for newly diagnosed chronic phase CML, and 500 mg once daily with food for previously treated patients. Dose adjustments may be required based on individual response, tolerability, and organ function.
Bosutinib should always be taken with food, as this significantly improves absorption and reduces gastrointestinal side effects. The tablets should be swallowed whole with a glass of water and should not be crushed, broken, or chewed. Consistent timing of the daily dose is recommended to maintain steady drug levels.
Adults
Newly Diagnosed Chronic Phase CML
The recommended starting dose is 400 mg once daily taken with food. This dose is based on the results of the BFORE trial, which demonstrated superior efficacy compared to imatinib 400 mg. Treatment should continue as long as the patient derives clinical benefit or until unacceptable toxicity occurs.
Previously Treated CML (Chronic, Accelerated, or Blast Phase)
The recommended starting dose is 500 mg once daily taken with food. This higher dose is used in patients who have been previously treated with one or more TKIs to overcome potential resistance mechanisms. Dose escalation to 600 mg once daily may be considered in patients who do not achieve an adequate response, provided there are no grade 3 or higher adverse reactions.
| Patient Group | Starting Dose | Maximum Dose | Special Notes |
|---|---|---|---|
| Newly diagnosed CP CML | 400 mg once daily | 600 mg once daily | Take with food; may escalate if inadequate response |
| Previously treated CML | 500 mg once daily | 600 mg once daily | Take with food; for CP, AP, or BP CML |
| Hepatic impairment (mild/moderate) | 200 mg once daily | Individualized | Close monitoring of liver function required |
| Renal impairment (moderate/severe) | 300 mg or 200 mg once daily | Individualized | Dose depends on severity; monitor renal function |
Children
Bosutinib Sandoz is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of bosutinib in pediatric patients have not been established in clinical trials. Pediatric CML is typically managed with imatinib or dasatinib, which have established dosing and safety data in younger patients. If a pediatric patient requires treatment with bosutinib, this should be considered on a case-by-case basis under the supervision of a specialist hematologist/oncologist.
Elderly
No specific dose adjustment is required for elderly patients based on age alone. However, elderly patients may have reduced hepatic and renal function, and they may be taking multiple concomitant medications, all of which could affect bosutinib pharmacokinetics and tolerability. In clinical trials, patients aged 65 years and older experienced a higher incidence of certain adverse events compared to younger patients. Close monitoring is recommended, and dose adjustments should be made as clinically indicated based on organ function and tolerability.
Missed Dose
If a dose of bosutinib is missed by more than 12 hours from the usual dosing time, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time. Patients should not take a double dose to make up for a missed one. If vomiting occurs after taking a dose, patients should not take an additional dose but should continue with the next scheduled dose. Consistent daily dosing is important for maintaining therapeutic drug levels and treatment efficacy.
Overdose
There is limited experience with bosutinib overdose in clinical studies. In the event of an overdose, treatment should be symptomatic and supportive. There is no specific antidote for bosutinib. Due to its high protein binding (approximately 94%), bosutinib is unlikely to be effectively removed by dialysis. Patients who have taken an overdose should be monitored closely for adverse effects, particularly gastrointestinal symptoms, hepatotoxicity, and myelosuppression. Medical attention should be sought immediately in the event of a suspected overdose.
Never adjust your bosutinib dose without consulting your oncologist. Dose modifications require careful assessment of your blood counts, liver function, kidney function, and treatment response. Abruptly stopping treatment can lead to disease progression.
What Are the Side Effects of Bosutinib Sandoz?
The most common side effects of bosutinib include diarrhea (affecting over 70% of patients), nausea, vomiting, abdominal pain, rash, fatigue, and abnormal liver function tests. Most side effects are manageable with supportive care and dose adjustments. Serious side effects requiring immediate medical attention include severe liver toxicity, significant myelosuppression, and fluid retention.
Like all medicines, Bosutinib Sandoz can cause side effects, although not everybody gets them. The side effect profile of bosutinib has been well characterized through extensive clinical trial programs involving thousands of patients. Understanding the frequency and nature of side effects helps patients and healthcare providers manage treatment effectively and recognize when medical intervention is needed.
Gastrointestinal side effects are the most frequently reported adverse events with bosutinib. Diarrhea, in particular, is very common and typically occurs early in treatment, often within the first few weeks. Most cases of diarrhea are mild to moderate in severity and can be managed with standard antidiarrheal medications such as loperamide. The incidence and severity of diarrhea generally decrease over time as the body adapts to the medication.
Hepatotoxicity is a clinically significant concern with bosutinib. Elevations in liver transaminases (ALT and AST) can occur, typically within the first three months of treatment. Regular monitoring of liver function is essential, and treatment may need to be interrupted or the dose reduced if significant elevations are detected. In rare cases, severe hepatotoxicity with jaundice and liver failure has been reported.
Very Common (affects more than 1 in 10 patients)
- Diarrhea (reported in over 70% of patients)
- Nausea
- Vomiting
- Abdominal pain
- Thrombocytopenia (low platelet count)
- Anemia (low red blood cell count)
- Neutropenia (low white blood cell count)
- Elevated ALT/AST (liver enzymes)
- Rash
- Fatigue
- Decreased appetite
- Headache
- Elevated lipase
Common (affects 1 to 10 in 100 patients)
- Upper respiratory tract infection
- Pneumonia
- Peripheral edema (swelling of hands/feet)
- Pleural effusion (fluid around the lungs)
- Pericardial effusion (fluid around the heart)
- Dizziness
- Elevated blood creatinine (kidney function marker)
- Pyrexia (fever)
- Pruritus (itching)
- Arthralgia (joint pain)
- Myalgia (muscle pain)
- Back pain
- Cough
- Dyspnea (shortness of breath)
Uncommon (affects 1 to 10 in 1,000 patients)
- Pancreatitis
- Hepatotoxicity with jaundice
- QTc prolongation
- Pericarditis
- Acute pulmonary edema
- Gastrointestinal hemorrhage
- Erythema multiforme
- Acute kidney injury
Rare (affects fewer than 1 in 1,000 patients)
- Liver failure
- Anaphylactic reaction
- Stevens-Johnson syndrome
- Pulmonary arterial hypertension
- Rhabdomyolysis
Contact your doctor or seek emergency medical care immediately if you experience: severe or persistent diarrhea (more than 6 episodes per day), signs of liver problems (yellowing of the skin or eyes, dark urine, severe abdominal pain), signs of bleeding or bruising, severe shortness of breath or chest pain, signs of infection with high fever, or a severe skin rash.
How Should You Store Bosutinib Sandoz?
Bosutinib Sandoz should be stored at room temperature below 30°C (86°F) in the original packaging to protect from moisture. Keep the tablets in their blister pack until ready to take. Do not use after the expiration date printed on the carton and blister.
Proper storage of bosutinib is essential to maintain the stability and efficacy of the medication. The film-coated tablets should be stored at temperatures not exceeding 30°C (86°F). They should be kept in the original carton and blister packaging to protect from light and moisture until the time of administration.
Do not store bosutinib in the bathroom or near a sink, as humidity can affect the stability of the tablets. Avoid leaving the medication in a car, especially during hot weather, as temperatures inside a vehicle can exceed safe storage limits. If traveling, keep the medication in a cool, dry place and in its original packaging.
As with all medications, keep Bosutinib Sandoz out of the reach and sight of children. The medication is a cytotoxic agent, and accidental ingestion by a child could have serious consequences. Do not use the medication after the expiry date (EXP) printed on the outer carton and blister. The expiry date refers to the last day of that month.
Do not dispose of unused or expired bosutinib through household waste or sewage. Cancer medications require special disposal procedures due to their potential environmental impact. Return any unused tablets to your pharmacist for safe disposal in accordance with local regulations. This helps protect the environment and prevents accidental exposure to others.
What Does Bosutinib Sandoz Contain?
Each Bosutinib Sandoz 100 mg film-coated tablet contains bosutinib (as bosutinib monohydrate) as the active ingredient, along with various inactive ingredients (excipients) that form the tablet core and film coating.
The active substance in Bosutinib Sandoz is bosutinib. Each film-coated tablet contains 100 mg of bosutinib (as bosutinib monohydrate). Bosutinib monohydrate is used in the formulation because it offers improved chemical stability compared to the anhydrous form. The molecular formula of bosutinib is C26H29Cl2N5O3, and it belongs to the chemical class of 4-anilino-3-quinolinecarbonitrile derivatives.
The tablet core typically contains excipients such as microcrystalline cellulose (a filler/binder), croscarmellose sodium (a disintegrant to help the tablet break apart in the gastrointestinal tract), sodium lauryl sulfate (a wetting agent to improve drug dissolution), poloxamer 188 (a surfactant), and povidone (a binder). Magnesium stearate is used as a lubricant to facilitate the manufacturing process.
The film coating contains ingredients such as polyvinyl alcohol, titanium dioxide (E171), macrogol/polyethylene glycol, talc, and iron oxide yellow (E172). The film coating serves multiple purposes: it protects the tablet from moisture, masks any unpleasant taste of the active ingredient, makes the tablet easier to swallow, and helps with identification of the product.
Patients with known allergies to any of the excipients should inform their healthcare provider. While excipient allergies are uncommon, sodium lauryl sulfate and certain colorants can occasionally cause reactions in sensitive individuals. The full list of excipients can be found on the package insert provided with the medication.
Frequently Asked Questions About Bosutinib Sandoz
Bosutinib Sandoz is a tyrosine kinase inhibitor used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adults. It is approved for both newly diagnosed chronic phase CML and for patients previously treated with one or more other tyrosine kinase inhibitors where imatinib, nilotinib, and dasatinib are not considered appropriate. It works by blocking the BCR-ABL protein that drives the growth of leukemia cells.
The most common side effects include diarrhea (occurring in over 70% of patients), nausea, vomiting, abdominal pain, rash, fatigue, low blood counts (thrombocytopenia, anemia, neutropenia), elevated liver enzymes, and decreased appetite. Diarrhea is typically most pronounced during the first few weeks and usually improves with supportive care such as loperamide.
Bosutinib Sandoz should be taken once daily with food. The tablets should be swallowed whole with a glass of water — do not crush, break, or chew them. Taking bosutinib with food is important as it increases absorption and helps reduce gastrointestinal side effects. The standard dose is 400 mg daily for newly diagnosed CML and 500 mg daily for previously treated patients, but your doctor will determine the right dose for you.
No, Bosutinib Sandoz must not be used during pregnancy. It may cause harm to the unborn baby. Women of childbearing potential must use effective contraception during treatment and for at least one month after the last dose. Men taking bosutinib should also use contraception. A pregnancy test should be performed before starting treatment. If you become pregnant while taking bosutinib, contact your doctor immediately.
Regular monitoring is essential. Blood counts should be checked weekly during the first month and then monthly. Liver function tests are recommended monthly for the first three months and as needed thereafter. Kidney function should also be monitored throughout treatment. Your oncologist will also schedule regular BCR-ABL molecular testing to assess your response to treatment, typically every three months initially.
Bosutinib is a second-generation tyrosine kinase inhibitor with a unique mechanism as a dual Src/ABL kinase inhibitor. Compared to imatinib, it achieves faster and deeper molecular responses. Unlike dasatinib, bosutinib has a lower risk of pleural effusion, and unlike nilotinib, it carries less cardiovascular risk. However, bosutinib typically causes more gastrointestinal side effects, particularly diarrhea, compared to other TKIs. It is active against many imatinib-resistant mutations but not the T315I mutation.
References
This article is based on evidence from the following peer-reviewed sources and international guidelines. All medical claims reflect current scientific consensus at Evidence Level 1A.
- European Medicines Agency (EMA). Bosulif (bosutinib) — Summary of Product Characteristics. Last updated 2024. Available at: EMA — Bosulif
- Brummendorf TH, Cortes JE, Milojkovic D, et al. Bosutinib (BOS) versus imatinib for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML): final 5-year results from the BFORE trial. Blood. 2022;140(Supplement 1):7562–7564. doi:10.1182/blood-2022-163151
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Chronic Myeloid Leukemia. Version 1.2024.
- Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966–984. doi:10.1038/s41375-020-0776-2
- Gambacorti-Passerini C, Cortes JE, Lipton JH, et al. Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica. 2018;103(8):1298–1307. doi:10.3324/haematol.2017.171249
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd list, 2023. Geneva: World Health Organization; 2023.
- Khoury HJ, Cortes JE, Kantarjian HM, et al. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012;119(15):3403–3412. doi:10.1182/blood-2011-11-390120
- European Society for Medical Oncology (ESMO). Chronic Myeloid Leukaemia: ESMO Clinical Practice Guidelines. Annals of Oncology. 2024;35(2):197–216.
Medical Editorial Team
This article has been written and medically reviewed by the iMedic Medical Editorial Team, a multidisciplinary group of licensed physicians specializing in oncology, hematology, and clinical pharmacology.
All content is reviewed according to international guidelines from ESMO, EMA, FDA, and NCCN. Our team follows the GRADE evidence framework and only references peer-reviewed sources with Evidence Level 1A.
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