June 25, 2016
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Sprycel

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Sprycel




Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to SPRYCEL at all doses tested in clinical studies including 324 patients with newly diagnosed chronic phase CML and in 2388 patients with imatinib-resistant or -intolerant chronic or advanced phase CML or Ph+ ALL. The median duration of therapy in 2712 SPRYCEL-treated patients was 19.2 months (range 0–93.2 months). In a randomized trial in patients with newly diagnosed chronic phase CML, the median duration of therapy was approximately 60 months. The median duration of therapy in 1618 patients with chronic phase CML was 29 months (range 0–92.9 months).

The median duration of therapy in 1094 patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0–93.2 months).

In the overall population of 2712 SPRYCEL-treated patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation.

In the randomized trial in patients with newly diagnosed chronic phase CML, drug was discontinued for adverse reactions in 16% of SPRYCEL-treated patients with a minimum of 60 months of follow-up. After a minimum of 60 months of follow-up, the cumulative discontinuation rate was 39%. Among the 1618 SPRYCEL-treated patients with chronic phase CML, drug-related adverse events leading to discontinuation were reported in 329 (20.3%) patients; among the 1094 SPRYCEL-treated patients with advanced phase CML or Ph+ ALL, drug-related adverse events leading to discontinuation were reported in 191 (17.5%) patients.

Adverse reactions reported in ≥ 10% of patients, and other adverse reactions of interest, in a randomized trial in patients with newly diagnosed chronic phase CML at a median follow-up of approximately 60 months are presented in Table 2.

Adverse reactions reported in ≥ 10% of patients treated at the recommended dose of 100 mg once daily (n=165), and other adverse reactions of interest, in a randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy at a median follow-up of approximately 84 months are presented in Table 4.

Drug-related serious adverse events (SAEs) were reported for 16.7% of SPRYCEL-treated patients in the randomized trial of patients with newly diagnosed chronic phase CML. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (5%).

Drug-related SAEs were reported for 26.1% of patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (10%).

Chronic Myeloid Leukemia (CML)

Adverse reactions (excluding laboratory abnormalities) that were reported in at least 10% of patients are shown in Table 2 for newly diagnosed patients with chronic phase CML and Tables 4 and 6 for CML patients with resistance or intolerance to prior imatinib therapy.

Table 2: Adverse Reactions Reported in ≥ 10% of Patients with Newly Diagnosed Chronic Phase CML (minimum of 60 months follow-up)

Preferred Term All Grades Grade 3/4
SPRYCEL
(n=258)
Imatinib
(n=258)
SPRYCEL
(n=258)
Imatinib
(n=258)
Percent (%) of Patients
Fluid retention 38 45 5 1
  Pleural effusion   28 1 3 0
  Superficial localized edema 14 38 0 < 1
  Pulmonary hypertension 5 < 1 1 0
  Generalized edema 4 7 0 0
  Pericardial effusion 4 1 1 0
  Congestive heart failure/ cardiac dysfunctiona 2 1 < 1 < 1
  Pulmonary edema 1 0 0 0
Diarrhea 22 23 1 1
Musculoskeletal pain 14 17 0 < 1
Rashb 14 18 0 2
Headache 14 11 0 0
Abdominal pain 11 8 0 1
Fatigue 11 12 < 1 0
Nausea 10 25 0 0
Myalgia 7 12 0 0
Arthralgia 7 10 0 < 1
Hemorrhagec 8 8 1 1
  Gastrointestinal bleeding 2 2 1 0
  Other bleedingd 6 6 0 < 1
  CNS bleeding < 1 < 1 0 < 1
Vomiting 5 12 0 0
Muscle spasms 5 21 0 < 1
a Includes cardiac failure acute, cardiac failure congestive, cardiomyopathy, diastolic dysfunction, ejection fraction decreased, and left ventricular dysfunction.
b Includes erythema, erythema multiforme, rash, rash generalized, rash macular, rash papular, rash pustular, skin exfoliation, and rash vesicular.
c Adverse reaction of special interest with < 10% frequency.
d Includes conjunctival hemorrhage, ear hemorrhage, ecchymosis, epistaxis, eye hemorrhage, gingival bleeding, hematoma, hematuria, hemoptysis, intra-abdominal hematoma, petechiae, scleral hemorrhage, uterine hemorrhage, and vaginal hemorrhage.

A comparison of cumulative rates of adverse reactions reported in ≥ 10% of patients with minimum follow-up of 1 and 5 years in a randomized trial of newly diagnosed patients with chronic phase CML treated with SPRYCEL are shown in Table 3.

Table 3: Adverse Reactions Reported in ≥ 10% of Patients with Newly Diagnosed Chronic Phase CML in the SPRYCEL-Treated Arm (n=258)

Preferred Term Minimum of 1 Year Follow-up Minimum of 5 Years Follow-up
All Grades Grade 3/4 All Grades Grade 3/4
Percent (%) of Patients
Fluid retention 19 1 38 5
  Pleural effusion 10 0 28 3
  Superficial localized edema 9 0 14 0
  Pulmonary hypertension 1 0 5 1
  Generalized edema 2 0 4 0
  Pericardial effusion  1 < 1 4 1
  Congestive heart failure/ cardiac dysfunctiona 2 < 1 2 < 1
  Pulmonary edema < 1 0 1 0
Diarrhea 17 < 1 22 1
Musculoskeletal pain 11 0 14 0
Rashb  11 0 14 0
Headache 12 0 14 0
Abdominal pain 7 0 11 0
Fatigue 8 < 1 11 < 1
Nausea 8 0 10 0
a Includes cardiac failure acute, cardiac failure congestive, cardiomyopathy, diastolic dysfunction, ejection fraction decreased, and left ventricular dysfunction.
b Includes erythema, erythema multiforme, rash, rash generalized, rash macular, rash papular, rash pustular, skin exfoliation, and rash vesicular.

At 60 months, there were 26 deaths in dasatinib-treated patients (10.1%) and 26 deaths in imatinib-treated patients (10.1%); 1 death in each group was assessed by the investigator as related to study therapy.

Table 4: Adverse Reactions Reported in ≥ 10% of Patients with Chronic Phase CML Resistant or Intolerant to Prior Imatinib Therapy (minimum of 84 months follow-up)

Preferred Term 100 mg Once Daily Chronic
(n=165)
All Grades Grade 3/4
Percent (%) of Patients
Fluid retention 48 7
Superficial localized edema 22 0
Pleural effusion 28 5
Generalized edema 4 0
Pericardial effusion 3 1
Pulmonary hypertension 2 1
Headache 33 1
Diarrhea 28 2
Fatigue 26 4
Dyspnea 24 2
Musculoskeletal pain 22 2
Nausea 18 1
Skin rasha 18 2
Myalgia 13 0
Arthralgia 13 1
Infection (including bacterial, viral, fungal, and non-specified) 13 1
Abdominal pain 12 1
Hemorrhage 12 1
Gastrointestinal bleeding 2 1
Pruritus 12 1
Pain 11 1
Constipation 10 1
a Includes drug eruption, erythema, erythema multiforme, erythrosis, exfoliative rash, generalized erythema, genital rash, heat rash, milia, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, skin exfoliation, skin irritation, urticaria vesiculosa, and rash vesicular.

Cumulative rates of selected adverse reactions that were reported over time in patients treated with the 100 mg once daily recommended starting dose in a randomized dose-optimization trial of imatinib-resistant or -intolerant patients with chronic phase CML are shown in Table 5.

Table 5: Selected Adverse Reactions Reported in Dose Optimization Trial (Imatinib-Intolerant or -Resistant Chronic Phase CML)a

Preferred Term Minimum of 2 Years Follow-up Minimum of 5 Years Follow-up Minimum of 7 Years Follow-up
All Grade Grades 3/4 All Grade Grades 3/4 All Grade Grades 3/4
Percent (%) of Patients
Diarrhea 27 2 28 2 28 2
Fluid retention 34 4 42 6 48 7
  Superficial edema 18 0 21 0 22 0
  Pleural effusion 18 2 24 4 28 5
  Generalized edema 3 0 4 0 4 0
  Pericardial effusion 2 1 2 1 3 1
Pulmonary hypertension 0 0 0 0 2 1
Hemorrhage 11 1 11 1 12 1
  Gastrointestinal bleeding 2 1 2 1 2 1
a Randomized dose-optimization trial results reported in the recommended starting dose of 100 mg once daily (n=165) population.

Table 6: Adverse Reactions Reported in ≥ 10% of Patients with Advanced Phase CML Resistant or Intolerant to Prior Imatinib Therapy

Preferred Term 140 mg Once Daily
Accelerated
(n=157)
Myeloid Blast
(n=74)

Lymphoid Blast
(n=33)

All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4
Percent (%) of Patients
Fluid retention 35 8 34 7 21 6
  Superficial localized edema 18 1 14 0 3 0
  Pleural effusion 21 7 20 7 21 6
  Generalized edema 1 0 3 0 0 0
  Pericardial effusion 3 1 0 0 0 0
  Congestive heart failure/cardiac dysfunctiona 0 0 4 0 0 0
  Pulmonary edema 1 0 4 3 0 0
Headache 27 1 18 1 15 3
Diarrhea 31 3 20 5 18 0
Fatigue 19 2 20 1 9 3
Dyspnea 20 3 15 3 3 3
Musculoskeletal pain 11 0 8 1 0 0
Nausea 19 1 23 1 21 3
Skin rashb 15 0 16 1 21 0
Arthralgia 10 0 5 1 0 0
Infection (including bacterial, viral, fungal, and non-specified) 10 6 14 7 9 0
Hemorrhage 26 8 19 9 24 9
  Gastrointestinal bleeding 8 6 9 7 9 3
  CNS bleeding 1 1 0 0 3 3
Vomiting 11 1 12 0 15 0
Pyrexia 11 2 18 3 6 0
Febrile neutropenia 4 4 12 12 12 12
a Includes ventricular dysfunction, cardiac failure, cardiac failure congestive, cardiomyopathy, congestive cardiomyopathy, diastolic dysfunction, ejection fraction decreased, and ventricular failure.
b Includes drug eruption, erythema, erythema multiforme, erythrosis, exfoliative rash, generalized erythema, genital rash, heat rash, milia, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, skin exfoliation, skin irritation, urticaria vesiculosa, and rash vesicular.

Laboratory Abnormalities

Myelosuppression was commonly reported in all patient populations. The frequency of Grade 3 or 4 neutropenia, thrombocytopenia, and anemia was higher in patients with advanced phase CML than in chronic phase CML (Tables 7 and 8). Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities.

In patients who experienced severe myelosuppression, recovery generally occurred following dose interruption or reduction; permanent discontinuation of treatment occurred in 2% of patients in a randomized trial of patients with newly diagnosed chronic phase CML and 5% of patients with resistance or intolerance to prior imatinib therapy [see WARNINGS AND PRECAUTIONS].

Grade 3 or 4 elevations of transaminases or bilirubin and Grade 3 or 4 hypocalcemia, hypokalemia, and hypophosphatemia were reported in patients with all phases of CML but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML. Elevations in transaminases or bilirubin were usually managed with dose reduction or interruption. Patients developing Grade 3 or 4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation. Laboratory abnormalities reported in patients with newly diagnosed chronic phase CML are shown in Table 7. There were no discontinuations of SPRYCEL therapy in this patient population due to biochemical laboratory parameters.

Table 7: CTC Grade 3/4 Laboratory Abnormalities in Patients with Newly Diagnosed Chronic Phase CML (minimum of 60 months follow-up)

  SPRYCEL
(n=258)
Imatinib
(n=258)
Percent (%) of Patients
Hematology Parameters
  Neutropenia 29 24
  Thrombocytopenia 22 14
  Anemia 13 9
Biochemistry Parameters
  Hypophosphatemia 7 31
  Hypokalemia 0 3
  Hypocalcemia 4 3
  Elevated SGPT (ALT) < 1 2
  Elevated SGOT (AST) < 1 1
  Elevated Bilirubin 1 0
  Elevated Creatinine 1 1
CTC grades: neutropenia (Grade 3 ≥ 0.5– < 1.0 109/L, Grade 4 < 0.5 109/L); thrombocytopenia (Grade 3 ≥ 25– < 50 109/L, Grade 4 < 25 109/L); anemia (hemoglobin Grade 3 ≥ 65– < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3–6 upper limit of normal range (ULN), Grade 4 > 6 ULN); elevated bilirubin (Grade 3 > 3–10 ULN, Grade 4 > 10 ULN); elevated SGOT or SGPT (Grade 3 > 5–20 ULN, Grade 4 > 20 ULN); hypocalcemia (Grade 3 < 7.0–6.0 mg/dL, Grade 4 < 6.0 mg/dL); hypophosphatemia (Grade 3 < 2.0–1.0 mg/dL, Grade 4 < 1.0 mg/dL); hypokalemia (Grade 3 < 3.0–2.5 mmol/L, Grade 4 < 2.5 mmol/L).

Laboratory abnormalities reported in patients with CML resistant or intolerant to imatinib who received the recommended starting doses of SPRYCEL are shown by disease phase in Table 8.

Table 8: CTC Grade 3/4 Laboratory Abnormalities in Clinical Studies of CML: Resistance or Intolerance to Prior Imatinib Therapy

  Chronic Phase CML 100 mg Once Daily
(n=165)
Advanced Phase CML 140 mg Once Daily
Accelerated Phase
(n=157)
Myeloid Blast Phase
(n=74)
Lymphoid Blast Phase
(n=33)
Percent (%) of Patients
Hematology Parameters*
  Neutropenia 36 58 77 79
  Thrombocytopenia 24 63 78 85
  Anemia 13 47 74 52
Biochemistry Parameters
  Hypophosphatemia 10 13 12 18
  Hypokalemia 2 7 11 15
  Hypocalcemia < 1 4 9 12
  Elevated SGPT (ALT) 0 2 5 3
  Elevated SGOT (AST) < 1 0 4 3
  Elevated Bilirubin < 1 1 3 6
  Elevated Creatinine 0 2 8 0
CTC grades: neutropenia (Grade 3 ≥ 0.5– < 1.0 109/L, Grade 4 < 0.5 109/L); thrombocytopenia (Grade 3 ≥ 25– < 50 109/L, Grade 4 < 25 109/L); anemia (hemoglobin Grade 3 ≥ 65– < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3–6 upper limit of normal range (ULN), Grade 4 > 6 ULN); elevated bilirubin (Grade 3 > 3–10 ULN, Grade 4 > 10 ULN); elevated SGOT or SGPT (Grade 3 > 5–20 ULN, Grade 4 > 20 ULN); hypocalcemia (Grade 3 < 7.0–6.0 mg/dL, Grade 4 < 6.0 mg/dL); hypophosphatemia (Grade 3 < 2.0–1.0 mg/dL, Grade 4 < 1.0 mg/dL); hypokalemia (Grade 3 < 3.0–2.5 mmol/L, Grade 4 < 2.5 mmol/L).
* Hematology parameters for 100 mg once-daily dosing in chronic phase CML reflects 60-month minimum follow-up.

Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative Grade 3 or 4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%).

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

A total of 135 patients with Ph+ ALL were treated with SPRYCEL in clinical studies. The median duration of treatment was 3 months (range 0.03–31 months). The safety profile of patients with Ph+ ALL was similar to those with lymphoid blast phase CML. The most frequently reported adverse reactions included fluid retention events, such as pleural effusion (24%) and superficial edema (19%), and gastrointestinal disorders, such as diarrhea (31%), nausea (24%), and vomiting (16%). Hemorrhage (19%), pyrexia (17%), rash (16%), and dyspnea (16%) were also frequently reported. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (11%), gastrointestinal bleeding (7%), febrile neutropenia (6%), and infection (5%).

Additional Pooled Data From Clinical Trials

The following additional adverse reactions were reported in patients in SPRYCEL CML and Ph+ ALL clinical studies at a frequency of ≥ 10%, 1%– < 10%, 0.1%– < 1%, or < 0.1%. These events are included on the basis of clinical relevance.

Gastrointestinal Disorders: 1%– < 10% – mucosal inflammation (including mucositis/ stomatitis), dyspepsia, abdominal distension, constipation, gastritis, colitis (including neutropenic colitis), oral soft tissue disorder; 0.1%– < 1% – ascites, dysphagia, anal fissure, upper gastrointestinal ulcer, esophagitis, pancreatitis, gastroesophageal reflux disease; < 0.1% – protein losing gastroenteropathy, ileus, acute pancreatitis, anal fistula.

General Disorders and Administration-Site Conditions: ≥ 10% – peripheral edema, face edema;1%– < 10% – asthenia, chest pain, chills; 0.1%– < 1% – malaise, other superficial edema; < 0.1% – gait disturbance.

Skin and Subcutaneous Tissue Disorders: 1%– < 10% – alopecia, acne, dry skin, hyperhidrosis, urticaria, dermatitis (including eczema); 0.1%– < 1% – pigmentation disorder, skin ulcer, bullous conditions, photosensitivity, nail disorder, neutrophilic dermatosis, panniculitis, palmar-plantar erythrodysesthesia syndrome, hair disorder; < 0.1% – leukocytoclastic vasculitis, skin fibrosis.

Respiratory, Thoracic, and Mediastinal Disorders: 1%– < 10% – lung infiltration, pneumonitis, cough; 0.1%– < 1% – asthma, bronchospasm, dysphonia, pulmonary arterial hypertension; < 0.1% – acute respiratory distress syndrome, pulmonary embolism.

Nervous System Disorders: 1%– < 10% – neuropathy (including peripheral neuropathy), dizziness, dysgeusia, somnolence; 0.1%– < 1% – amnesia, tremor, syncope, balance disorder; < 0.1% – convulsion, cerebrovascular accident, transient ischemic attack, optic neuritis, VIIth nerve paralysis, dementia, ataxia.

Blood and Lymphatic System Disorders: 0.1%– < 1% – lymphadenopathy, lymphopenia; < 0.1% – aplasia pure red cell.

Musculoskeletal and Connective Tissue Disorders: 1%– < 10% – muscular weakness, musculoskeletal stiffness; 0.1%– < 1% – rhabdomyolysis, tendonitis, muscle inflammation, osteonecrosis, arthritis.

Investigations: 1%– < 10% – weight increased, weight decreased; 0.1%– < 1% – blood creatine phosphokinase increased, gamma-glutamyltransferase increased.

Infections and Infestations: 1%– < 10% – pneumonia (including bacterial, viral, and fungal), upper respiratory tract infection/inflammation, herpes virus infection, enterocolitis infection, sepsis (including fatal outcomes [0.2%]).

Metabolism and Nutrition Disorders: 1%– < 10% – appetite disturbances, hyperuricemia; 0.1%– < 1% – hypoalbuminemia, tumor lysis syndrome, dehydration, hypercholesterolemia; < 0.1% – diabetes mellitus.

Cardiac Disorders: 1%– < 10% – arrhythmia (including tachycardia), palpitations; 0.1%– < 1% – angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia), electrocardiogram T-wave abnormal, troponin increased; < 0.1% – cor pulmonale, myocarditis, acute coronary syndrome, cardiac arrest, electrocardiogram PR prolongation, coronary artery disease, pleuropericarditis.

Eye Disorders: 1%– < 10% – visual disorder (including visual disturbance, vision blurred, and visual acuity reduced), dry eye; 0.1%– < 1% – conjunctivitis, visual impairment, photophobia, lacrimation increased.

Vascular Disorders: 1%– < 10% – flushing, hypertension; 0.1%– < 1% – hypotension, thrombophlebitis, thrombosis; < 0.1% – livedo reticularis, deep vein thrombosis, embolism.

Psychiatric Disorders: 1%– < 10% – insomnia, depression; 0.1%– < 1% – anxiety, affect lability, confusional state, libido decreased.

Pregnancy, Puerperium, and Perinatal Conditions: < 0.1% – abortion.

Reproductive System and Breast Disorders: 0.1%– < 1% – gynecomastia, menstrual disorder.

Injury, Poisoning, and Procedural Complications: 1%– < 10% – contusion.

Ear and Labyrinth Disorders: 1%– < 10% – tinnitus; 0.1%– < 1% – vertigo, hearing loss.

Hepatobiliary Disorders: 0.1%– < 1% – cholestasis, cholecystitis, hepatitis.

Renal and Urinary Disorders: 0.1%– < 1% – urinary frequency, renal failure, proteinuria; < 0.1% – renal impairment.

Immune System Disorders: 0.1%– < 1% – hypersensitivity (including erythema nodosum).

Endocrine Disorders: 0.1%– < 1% – hypothyroidism; < 0.1% – hyperthyroidism, thyroiditis.

Postmarketing Experience

The following additional adverse reactions have been identified during postapproval use of SPRYCEL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac disorders: atrial fibrillation/atrial flutter

Respiratory, thoracic, and mediastinal disorders: interstitial lung disease

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome

Read the Sprycel (dasatinib) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Drugs That May Increase Dasatinib Plasma Concentrations

CYP3A4 Inhibitors

Dasatinib is a CYP3A4 substrate. In a trial of 18 patients with solid tumors, 20-mg SPRYCEL once daily coadministered with 200 mg of ketoconazole twice daily increased the dasatinib Cmax and AUC by four- and five-fold, respectively. Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 may increase exposure to dasatinib and should be avoided. In patients receiving treatment with SPRYCEL, close monitoring for toxicity and a SPRYCEL dose reduction should be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [see DOSAGE AND ADMINISTRATION].

Drugs That May Decrease Dasatinib Plasma Concentrations

CYP3A4 Inducers

When a single morning dose of SPRYCEL was administered following 8 days of continuous evening administration of 600 mg of rifampin, a potent CYP3A4 inducer, the mean Cmax and AUC of dasatinib were decreased by 81% and 82%, respectively. Alternative agents with less enzyme induction potential should be considered. If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase in SPRYCEL should be considered [see DOSAGE AND ADMINISTRATION].

Antacids

Nonclinical data demonstrate that the solubility of dasatinib is Ph dependent. In a trial of 24 healthy subjects, administration of 30 mL of aluminum hydroxide/magnesium hydroxide 2 hours prior to a single 50-mg dose of SPRYCEL was associated with no relevant change in dasatinib AUC; however, the dasatinib Cmax increased 26%. When 30 mL of aluminum hydroxide/magnesium hydroxide was administered to the same subjects concomitantly with a 50-mg dose of SPRYCEL, a 55% reduction in dasatinib AUC and a 58% reduction in Cmax were observed. Simultaneous administration of SPRYCEL with antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of SPRYCEL.

H2 Antagonists/Proton Pump Inhibitors

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g., famotidine and omeprazole) is likely to reduce dasatinib exposure. In a trial of 24 healthy subjects, administration of a single 50-mg dose of SPRYCEL 10 hours following famotidine reduced the AUC and Cmax of dasatinib by 61% and 63%, respectively. In a trial of 14 healthy subjects, administration of a single 100-mg dose of SPRYCEL 22 hours following a 40-mg omeprazole dose at steady state reduced the AUC and Cmax of dasatinib by 43% and 42%, respectively. The concomitant use of H2 antagonists or proton pump inhibitors with SPRYCEL is not recommended. The use of antacids (at least 2 hours prior to or 2 hours after the dose of SPRYCEL) should be considered in place of H2 antagonists or proton pump inhibitors in patients receiving SPRYCEL therapy.

Drugs That May Have Their Plasma Concentration Altered By Dasatinib

CYP3A4 Substrates

Single-dose data from a trial of 54 healthy subjects indicate that the mean Cmax and AUC of simvastatin, a CYP3A4 substrate, were increased by 37% and 20%, respectively, when simvastatin was administered in combination with a single 100-mg dose of SPRYCEL. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving SPRYCEL.

Read the Sprycel Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 6/24/2016

Side Effects
Interactions

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