Thursday, December 25, 2014
Home Information On Drugs
Sprycel

Sprycel

Sprycel Drug Description


SPRYCEL®
(dasatinib) Tablet for Oral Use

DRUG DESCRIPTION

SPRYCEL (dasatinib) is a kinase inhibitor. The chemical name for dasatinib is N-(2-chloro-6-methylphenyl)-2- [ [6- [4-(2-hydroxyethyl)-1 -piperazinyl] -2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate. The molecular formula is C22H26C1N7O2S•H2O, which corresponds to a formula weight of 506.02 (monohydrate). The anhydrous free base has a molecular weight of 488.01. Dasatinib has the following chemical structure:

 


Dasatinib is a white to off-white powder. The drug substance is insoluble in water and slightly soluble in ethanol and methanol. SPRYCEL tablets are white to off-white, biconvex, film-coated tablets containing dasatinib, with the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. The tablet coating consists of hypromellose, titanium dioxide, and polyethylene glycol.

 

What are the possible side effects of dasatinib (Sprycel)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • pale skin, weakness;
  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • fever, chills, body aches, flu symptoms;
  • black, bloody, or tarry stools;
  • vomit that looks like blood or coffee grounds;
  • sudden numbness or weakness, especially on one...

Read All Potential Side Effects and See Pictures of Sprycel »

 

What are the precautions when taking dasatinib (Sprycel)?

Before taking dasatinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as lactose), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems, heart problems (e.g., irregular heartbeat), liver problems.

Dasatinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have...

 

 

Sprycel

Sprycel Indications & Dosage


INDICATIONS

SPRYCEL® (dasatinib) is indicated for the treatment of adults with

  • newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic response and major molecular response rates [see Clinical Studies]. The trial is ongoing and further data will be required to determine long-term outcome.
  • chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy.

DOSAGE AND ADMINISTRATION

The recommended starting dosage of SPRYCEL for chronic phase CML is 100 mg administered orally once daily. The recommended starting dosage of SPRYCEL for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg administered orally once daily. Tablets should not be crushed or cut; they should be swallowed whole. SPRYCEL can be taken with or without a meal, either in the morning or in the evening.

In clinical studies, treatment with SPRYCEL was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment after the achievement of a complete cytogenetic response (CCyR) has not been investigated.

Dose Modification

Concomitant Strong CYP3A4 inducers: The use of concomitant strong CYP3A4 inducers may decrease dasatinib plasma concentrations and should be avoided (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital). St. John's Wort may decrease dasatinib plasma concentrations unpredictably and should be avoided. If patients must be coadministered a strong CYP3 A4 inducer, based on pharmacokinetic studies, a SPRYCEL dose increase should be considered. If the dose of SPRYCEL is increased, the patient should be monitored carefully for toxicity [see DRUG INTERACTIONS].

Concomitant Strong CYP3A4 inhibitors: CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) may increase dasatinib plasma concentrations. Grapefruit juice may also increase plasma concentrations of dasatinib and should be avoided.

Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible, is recommended. If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease should be considered. Based on pharmacokinetic studies, a dose decrease to 20 mg daily should be considered for patients taking SPRYCEL 100 mg daily. For patients taking SPRYCEL 140 mg daily, a dose decrease to 40 mg daily should be considered. These reduced doses of SPRYCEL are predicted to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors. However, there are no clinical data with these dose adjustments in patients receiving strong CYP3A4 inhibitors. If SPRYCEL is not tolerated after dose reduction, either the strong CYP3A4 inhibitor must be discontinued, or SPRYCEL should be stopped until treatment with the inhibitor has ceased. When the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the SPRYCEL dose is increased. [See DRUG INTERACTIONS.]

Dose Escalation

In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended starting dosage.

Dose Adjustment for Adverse Reactions

Myelosuppression

In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression. Guidelines for dose modifications are summarized in Table 1.

Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia


Non-hematological adverse reactions

If a severe non-hematological adverse reaction develops with SPRYCEL use, treatment must be withheld until the event has resolved or improved. Thereafter, treatment can be resumed as appropriate at a reduced dose depending on the initial severity of the event.

HOW SUPPLIED

Dosage Forms and Strengths

SPRYCEL (dasatinib) Tablets are available as 20-mg, 50-mg, 70-mg, 80-mg, 100-mg, and 140-mg white to off-white, biconvex, film-coated tablets.

SPRYCEL® (dasatinib) tablets are available as described in Table 9.

Table 9: SPRYCEL Trade Presentations

NDC Number Strength Description Tablets per Bottle
0003-0527-11 20 mg white to off-white, biconvex, round, film-coated tablet with "BMS" debossed on one side and "527" on the other side 60
0003-0528-11 50 mg white to off-white, biconvex, oval, film-coated tablet with "BMS" debossed on one side and "528" on the other side 60
0003-0524-11 70 mg white to off-white, biconvex, round, film-coated tablet with "BMS" debossed on one side and "524" on the other side 60
0003-0855-22 80 mg white to off-white, biconvex, triangle, film-coated tablet with "BMS" and "80" (BMS over 80) debossed on one side and "855" on the other side 30
0003-0852-22 100 mg white to off-white, biconvex, oval, film-coated tablet with "BMS 100" debossed on one side and "852" on the other side 30
0003-0857-22 140 mg white to off-white, biconvex, round, film-coated tablet with "BMS" and "140" (BMS over 140) debossed on one side and "857" on the other side 30

Storage

SPRYCEL® tablets should be stored at 20° to 25°C (68° to 77°F); excursions permitted between 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Handling and Disposal

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [see References].

SPRYCEL (dasatinib) tablets consist of a core tablet (containing the active drug substance), surrounded by a film coating to prevent exposure of pharmacy and clinical personnel to the active drug substance. However, if tablets are inadvertently crushed or broken, pharmacy and clinical personnel should wear disposable chemotherapy gloves. Personnel who are pregnant should avoid exposure to crushed or broken tablets.

Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA.

 

Sprycel

Sprycel Side Effects & Drug Interactions


SIDE EFFECTS

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

  • Myelosuppression [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
  • Bleeding related events [see WARNINGS AND PRECAUTIONS].
  • Fluid retention [see WARNINGS AND PRECAUTIONS].
  • QT prolongation [see WARNINGS AND PRECAUTIONS].
  • Congestive heart failure, left ventricular dysfunction, and myocardial infarction [see WARNINGS AND PRECAUTIONS].
  • Pulmonary Arterial Hypertension [see WARNINGS AND PRECAUTIONS].

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 in clinical studies including 25 8 patients with newly diagnosed chronic phase CML and in 2182 patients with imatinib resistant or intolerant CML or Ph+ ALL.

In the newly diagnosed chronic phase CML trial, the median duration of therapy was 18 months; the median average daily dose was 99 mg.

In the imatinib resistant or intolerant CML or Ph+ALL clinical trials, patients had a minimum of 2 years follow-up (starting dosage lOOmg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily). Among patients with chronic phase CML and resistance or intolerance to prior imatinib therapy, the median duration of treatment with SPRYCEL 100 mg once daily was 24 months (range 1-33 months). The median duration of treatment with SPRYCEL 140 mg once daily was 15 months (range 0.03-36 months) for accelerated phase CML, 3 months (range 0.03-29 months) for myeloid blast phase CML, and 3 months (range 0.1-10 months) for lymphoid blast CML.

The majority of SPRYCEL-treated patients experienced adverse reactions at some time. In the newly diagnosed chronic phase CML trial, drug was discontinued for adverse reactions in 6% of SPRYCEL-treated patients. Among patients with resistance or intolerance to prior imatinib therapy, the rates of discontinuation for adverse reaction were 15% in chronic phase CML, 16% in accelerated phase CML, 15% in myeloid blast phase CML, 8% in lymphoid blast phase CML, and 8% in Ph+ ALL. In a dose-optimization study in patients with resistance or intolerance to prior imatinib therapy and chronic phase CML, the rate of discontinuation for adverse reaction was lower in patients treated with 100 mg once daily than in patients treated with other dosing regimens (10% and 16%, respectively).

The most frequently reported adverse reactions reported in ≥ 10% of patients in newly diagnosed chronic phase CML included myelosuppression, fluid retention events (pleural effusion, superficial localized edema, generalized edema), diarrhea, headache, musculoskeletal pain, and rash. Pleural effusions were reported in 31 patients (see Table 2).

The most frequently reported adverse reactions reported in ≥ 20% of patients with resistance or intolerance to prior imatinib therapy included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage.

The most frequently reported serious adverse reactions in patients with newly diagnosed chronic phase CML included pleural effusion (2%), hemorrhage (2%), congestive heart failure (1%), and pyrexia (1%). The most frequently reported serious adverse reactions in patients with resistance or intolerance to prior imatinib therapy included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and CNS hemorrhage (1%).

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 Table 3 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

Preferred Term All Grades Grade 3/4
SPRYCEL
(n=258)
Imatinib
(n=258)
SPRYCEL
(n=258)
Imatinib
(n=258)
Percent (%) of Patients
Fluid retention 23 43 1 1
Pleural effusion 12 0 < 1 0
Superficial localized edema 10 36 0 < 1
Generalized edema 3 7 0 0
Congestive heart failure/cardiac dysfunctiona 2 1 < 1 < 1
Pericardial effusion 2 < 1 < 1 0
Pulmonary hypertension 1 0 0 0
Pulmonary edema < 1 0 0 0
Diarrhea 18 19 < 1 1
Headache 12 10 0 0
Musculoskeletal pain 12 16 0 < 1
Rashb 11 17 0 1
Nausea 9 21 0 0
Fatigue 8 11 < 1 0
Myalgia 6 12 0 0
Hemorrhagec 6 5 1 1
Gastrointestinal bleeding 2 < 1 1 0
Other bleedingd 5 5 0 1
CNS bleeding 0 < 1 0 < 1
Vomiting 5 10 0 0
Muscle inflammation 4 19 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.

Table 3: Adverse Reactions Reported in ≥ 10% of Patients with CML Resistant or Intolerant to Prior Imatinib Therapy


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 4 and 5). 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 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 transaminase 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 transaminase 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 4. There were no discontinuations of SPRYCEL therapy in this patient population due to biochemical laboratory parameters.

Table 4: CTC Grade 3/4 Laboratory Abnormalities in Patients with Newly Diagnosed Chronic Phase CML

SPRYCEL
(n=258)
Imatinib
(n=258)
Percent (%) of Patients
Hematology Parameters
Neutropenia 22 20
Thrombocytopenia 19 10
Anemia 11 7
Biochemistry Parameters
Hypophosphatemia 5 24
Hypokalemia 0 2
Hypocalcemia 3 2
Elevated SGPT (ALT) < 1 1
Elevated SCOT (AST) < 1 1
Elevated Bilirubin 1 0
Elevated Creatinine < 1 1
CTC grades: neutropenia (Grade 3 ≥ 0.5- < 1.0 x 109/L, Grade 4 < 0.5 x 109/L); thrombocytopenia (Grade 3 ≥ 25- < 50 x 109/L, Grade 4 < 25 x 109/L); anemia (hemoglobin Grade 3 ≥ 65- < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3-6 x upper limit of normal range (ULN), Grade 4 > 6 x ULN); elevated bilirubin (Grade 3 > 3-10 x ULN, Grade 4 > 10 x ULN); elevated SGOT or SGPT (Grade 3 > 5-20 x ULN, Grade 4 > 20 x 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 5.

Table 5: CTC Grade 3/4 Laboratory Abnormalities in Clinical Studies of CML: Resistance or Intolerance to Prior Imatinib Therapy

Chronic Phase CML Advanced Phase CML
100 mg Once Daily
(n=165)
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 23 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 SCOT (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 x 109/L, Grade 4 < 0.5 x 109/L); thrombocytopenia (Grade 3 ≥ 25- < 50 x 109/L, Grade 4 < 25 x 109/L); anemia (hemoglobin Grade 3 ≥ 65- < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3-6 x upper limit of normal range (ULN), Grade 4 > 6 x ULN); elevated bilirubin (Grade 3 > 3-10 x ULN, Grade 4 > 10 x ULN); elevated SGOT or SGPT (Grade 3 > 5-20 x ULN, Grade 4 > 20 x 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).

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. The most frequently reported serious adverse reactions included pleural effusion (11%), gastrointestinal bleeding (7%), febrile neutropenia (6%), infection (5%), pyrexia (4%), pneumonia (3%), diarrhea (3%), nausea (2%), vomiting (2%), and colitis (2%).

Additional Data From Clinical Trials

The following adverse reactions were reported in patients in the SPRYCEL clinical studies at a frequency of 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; < 0.1%- protein losing gastroenteropathy.

General Disorders and Administration Site Conditions: 1%- < 10% — asthenia, pain, chest pain, chills; 0.1%- < 1% - malaise, temperature intolerance.

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

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

Nervous System Disorders: 1%- < 10% - neuropathy (including peripheral neuropathy), dizziness, dysgeusia, somnolence; 0.1%- < 1% - amnesia, tremor, syncope; < 0.1% -convulsion, cerebrovascular accident, transient ischemic attack, optic neuritis.

Blood and Lymphatic System Disorders: 1%- < 10% - pancytopenia; < 0.1% - aplasia pure red cell.

Musculoskeletal and Connective Tissue Disorders: 1%- < 10% - muscular weakness; 0.1%- < 1% - musculoskeletal stiffness, rhabdomyolysis; < 0.1%- tendonitis.

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

Infections and Infestations: 1%- < 10% - pneumonia (including bacterial, viral, and fungal), upper respiratory tract infection/inflammation, herpes virus infection, enterocolitis infection; 0.1%- < 1% Asepsis (including fatal outcomes).

Metabolism and Nutrition Disorders: 1%- < 10% - anorexia, appetite disturbances; 0.1%- < 1% - hyperuricemia, hypoalbuminemia.

Cardiac Disorders: 1%- < 10% - arrhythmia (including tachycardia), palpitations; 0.1%- < 1% - angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia); < 0.1%- cor pulmonale, myocarditis, acute coronary syndrome.

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

Vascular Disorders: 1%- < 10% - flushing, hypertension; 0.1%- < 1% - hypotension, thrombophlebitis; < 0.1%- livedo reticularis.

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

Reproductive System and Breast Disorders: 0.1%- < 1% - gynecomastia, menstruation irregular.

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

Ear and Labyrinth Disorders: 1%- < 10% - tinnitus; 0.1%- < 1% - vertigo.

Hepatobiliary Disorders: 0.7%- < 7%-cholestasis, cholecystitis, hepatitis.

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

Neoplasms Benign, Malignant, and Unspecified: 0.1%- < 1% - tumor lysis syndrome.

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

Postmarketing Experience

The following additional adverse reactions have been identified during post approval 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

Vascular disorders: thrombosis/embolism (including pulmonary embolism, deep vein thrombosis)

Respiratory, thoracic, and mediastinal disorders: interstitial lung disease, pulmonary arterial hypertension

DRUG INTERACTIONS

Drugs That May Increase Dasatinib Plasma Concentrations

CYP3A4 Inhibitors: Dasatinib is a CYP3A4 substrate. In a study 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 Qnax 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 CYP3 A4 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 study 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 C^x 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 (eg, famotidine and omeprazole) is likely to reduce dasatinib exposure. In a study of 24 healthy subjects, administration of a single 50-mg dose of SPRYCEL 10 hours following famotidine reduced the AUC and Qmx of dasatinib by 61% and 63%, respectively. In a study 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 study of 54 healthy subjects indicate that the mean Qnax 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.

 

 

Sprycel

 

Sprycel Warnings & Precautions


WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Myelosuppression

Treatment with SPRYCEL is associated with severe (NCI CTC Grade 3 or 4) thrombocytopenia, neutropenia, and anemia. Their occurrence is more frequent in patients with advanced phase CML or Ph+ALL than in chronic phase CML. In a dose-optimization study in patients with resistance or intolerance to prior imatinib therapy and chronic phase CML, Grade 3 or 4 myelosuppression was reported less frequently in patients treated with 100 mg once daily than in patients treated with other dosing regimens.

Perform complete blood counts weekly for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding SPRYCEL temporarily or dose reduction [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].

Bleeding Related Events

In addition to causing thrombocytopenia in human subjects, dasatinib caused platelet dysfunction in vitro. In all clinical studies, severe central nervous system (CNS) hemorrhages, including fatalities, occurred in 1% of patients receiving SPRYCEL. Severe gastrointestinal hemorrhage, including fatalities, occurred in 4% of patients and generally required treatment interruptions and transfusions. Other cases of severe hemorrhage occurred in 2% of patients. Most bleeding events were associated with severe thrombocytopenia.

Patients were excluded from participation in initial SPRYCEL clinical studies if they took medications that inhibit platelet function or anticoagulants. In subsequent trials, the use of anticoagulants, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs) was allowed concurrently with SPRYCEL if the platelet count was > 50,000-75,000 per microliter. Exercise caution if patients are required to take medications that inhibit platelet function or anticoagulants.

Fluid Retention

SPRYCEL is associated with fluid retention. In clinical trials, severe fluid retention was reported in up to 10% of patients. Ascites and generalized edema were each reported in < 1% of patients. Severe pulmonary edema was reported in 1% of patients. Patients who develop symptoms suggestive of pleural effusion, such as dyspnea or dry cough, should be evaluated by chest X-ray. Severe pleural effusion may require thoracentesis and oxygen therapy. Fluid retention events were typically managed by supportive care measures that include diuretics or short courses of steroids. In dose-optimization studies, fluid retention events were reported less frequently with once daily dosing than with other dosing regimens.

QT Prolongation

In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarization (QT interval). Of the 2440 patients with CML treated with SPRYCEL in clinical studies, 15 patients ( < 1%) had QTc prolongation reported as an adverse reaction. Twenty-two patients (1%) experienced a QTcF > 500ms. In 865 patients with leukemia treated with SPRYCEL in five Phase 2 single-arm studies, the maximum mean changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 ms to 13.4 ms.

Administer SPRYCEL with caution to patients who have or may develop prolongation of QTc. These include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy. Correct hypokalemia or hypomagnesemia prior to SPRYCEL administration.

Congestive Heart Failure, Left Ventricular Dysfunction, and Myocardial Infarction

Cardiac adverse reactions were reported in 5.8% of 258 patients taking SPRYCEL, including 1.6% of patients with cardiomyopathy, heart failure congestive, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.

Pulmonary Arterial Hypertension

SPRYCEL may increase the risk of developing pulmonary arterial hypertension (PAH) which may occur anytime after initiation, including after more than one year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of SPRYCEL. Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should be permanently discontinued.

Use in Pregnancy

SPRYCEL may cause fetal harm when administered to a pregnant woman. In nonclinical studies, at plasma concentrations below those observed in humans receiving therapeutic doses of dasatinib, embryo-fetal toxicities, including skeletal malformations, were observed in rats and rabbits. There are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SPRYCEL [see Use In Specific Populations].

Patient Counseling Information

See FDA-Approved Patient Labeling.

Bleeding

Patients should be informed of the possibility of serious bleeding and to report immediately any signs or symptoms suggestive of hemorrhage (unusual bleeding or easy bruising).

Myelosuppression

Patients should be informed of the possibility of developing low blood cell counts; they should be instructed to report immediately should fever develop, particularly in association with any suggestion of infection.

Fluid Retention

Patients should be informed of the possibility of developing fluid retention (swelling, weight gain, or shortness of breath) and to seek medical attention if those symptoms arise.

Pregnancy

Patients should be informed that dasatinib may cause fetal harm when administered to a pregnant woman. Women should be advised of the potential hazard to the fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if the patient becomes pregnant while taking SPRYCEL, the patient should be apprised of the potential hazard to the fetus [see WARNINGS AND PRECAUTIONS].

Gastrointestinal Complaints

Patients should be informed that they may experience nausea, vomiting, or diarrhea with SPRYCEL. If these symptoms are significant, they should seek medical attention.

Pain

Patients should be informed that they may experience headache or musculoskeletal pain with SPRYCEL. If these symptoms are significant, they should seek medical attention.

Fatigue

Patients should be informed that they may experience fatigue with SPRYCEL. If this symptom is significant, they should seek medical attention.

Rash

Patients should be informed that they may experience skin rash with SPRYCEL. If this symptom is significant, they should seek medical attention.

Lactose

Patients should be informed that SPRYCEL contains 135 mg of lactose monohydrate in a 100-mg daily dose and 189 mg of lactose monohydrate in a 140-mg daily dose.

Missed Dose

If the patient misses a dose of SPRYCEL, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year carcinogenicity study, rats were administered oral doses of dasatinib at 0.3, 1, and 3 mg/kg/day. The highest dose resulted in a plasma drug exposure (AUC) level equivalent to human exposure at 70 mg twice daily. Dasatinib induced a statistically significant increase in the combined incidence of squamous cell carcinomas and papillomas in the uterus and cervix of high-dose females and prostate adenoma in low-dose males.

Dasatinib was clastogenic when tested in vitro in Chinese hamster ovary cells, with and without metabolic activation. Dasatinib was not mutagenic when tested in an in vitro bacterial cell assay (Ames test) and was not genotoxic in an in vivo rat micronucleus study.

The effects of dasatinib on male and female fertility have not been studied. However, results of repeat-dose toxicity studies in multiple species indicate the potential for dasatinib to impair reproductive function and fertility. Effects evident in male animals included reduced size and secretion of seminal vesicles, and immature prostate, seminal vesicle, and testis. The administration of dasatinib resulted in uterine inflammation and mineralization in monkeys, and cystic ovaries and ovarian hypertrophy in rodents.

Use In Specific Populations

Pregnancy

Pregnancy Category D

SPRYCEL may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if the patient becomes pregnant while taking SPRYCEL, the patient should be apprised of the potential hazard to the fetus.

In nonclinical studies, at plasma concentrations below those observed in humans receiving therapeutic doses of dasatinib, embryo-fetal toxicities were observed in rats and rabbits. Fetal death was observed in rats. In both rats and rabbits, the lowest doses of dasatinib tested (rat: 2.5 mg/kg/day [15 mg/m2/day] and rabbit: 0.5 mg/kg/day [6 mg/m2/day]) resulted in embryo-fetal toxicities. These doses produced maternal AUCs of 105 ng·hr/mL (0.3-fold the human AUC in females at a dose of 70 mg twice daily) and 44 ng·hr/mL (0.1-fold the human AUC) in rats and rabbits, respectively. Embryo-fetal toxicities included skeletal malformations at multiple sites (scapula, humerus, femur, radius, ribs, and clavicle), reduced ossification (sternum; thoracic, lumbar, and sacral vertebrae; forepaw phalanges; pelvis; and hyoid body), edema, and microhepatia.

Nursing Mothers

It is unknown whether SPRYCEL is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from SPRYCEL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of SPRYCEL in patients less than 18 years of age have not been established.

Geriatric Use

In the newly diagnosed chronic phase CML study, 25 patients (10%) were 65 years of age and over and 7 patients (3%) were 75 years of age and over. Of the 2182 patients in clinical studies of SPRYCEL with resistance or intolerance to imatinib therapy, 547 (25%) were 65 years of age and over and 105 (5%) were 75 years of age and over. No differences in efficacy were observed between older and younger patients. Compared to patients under age 65 years, patients aged 65 years and older are more likely to experience toxicity.

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of dasatinib was evaluated in healthy volunteers with normal liver function and patients with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment. Compared to the healthy volunteers with normal hepatic function, the dose normalized pharmacokinetic parameters were decreased in the patients with hepatic impairment.

No dosage adjustment is necessary in patients with hepatic impairment [see CLINICAL PHARMACOLOGY]. Caution is recommended when administering SPRYCEL to patients with hepatic impairment.

Renal Impairment

There are currently no clinical studies with SPRYCEL in patients with impaired renal function. Less than 4% of dasatinib and its metabolites are excreted via the kidney.

 

 

Sprycel

Sprycel Overdosage & Contraindications


OVERDOSE

Experience with overdose of SPRYCEL in clinical studies is limited to isolated cases. Overdosage of 280 mg per day for 1 week was reported in two patients and both developed severe myelosuppression and bleeding. Since SPRYCEL is associated with severe myelosuppression, [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS], patients who ingested more than the recommended dosage should be closely monitored for myelosuppression and given appropriate supportive treatment.

Acute overdose in animals was associated with cardiotoxicity. Evidence of cardiotoxicity included ventricular necrosis and valvular/ventricular/atrial hemorrhage at single doses ≥ 100 mg/kg (600 mg/m2) in rodents. There was a tendency for increased systolic and diastolic blood pressure in monkeys at single doses ≥ 10 mg/kg (120 mg/m2).

CONTRAINDICATIONS

None.

 

Sprycel

 

Sprycel Clinical Pharmacology


CLINICAL PHARMACOLOGY

Mechanism of Action

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase.

In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.

Pharmacokinetics

Absorption

Maximum plasma concentrations (Cmax) of dasatinib are observed between 0.5 and 6 hours (Tmax) following oral administration. Dasatinib exhibits dose proportional increases in AUC and linear elimination characteristics over the dose range of 15 mg to 240 mg/day. The overall mean terminal half-life of dasatinib is 3-5 hours.

Data from a study of 54 healthy subjects administered a single, 100-mg dose of dasatinib 30 minutes following consumption of a high-fat meal resulted in a 14% increase in the mean AUC of dasatinib. The observed food effects were not clinically relevant.

Distribution

In patients, dasatinib has an apparent volume of distribution of 2505 L, suggesting that the drug is extensively distributed in the extravascular space. Binding of dasatinib and its active metabolite to human plasma proteins in vitro was approximately 96% and 93%, respectively, with no concentration dependence over the range of 100-500 ng/mL.

Metabolism

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. CYP3A4 was the primary enzyme responsible for the formation of the active metabolite. Flavin-containing monooxygenase 3 (FMO-3) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes are also involved in the formation of dasatinib metabolites.

The exposure of the active metabolite, which is equipotent to dasatinib, represents approximately 5% of the dasatinib AUC. This indicates that the active metabolite of dasatinib is unlikely to play a major role in the observed pharmacology of the drug. Dasatinib also had several other inactive oxidative metabolites.

Dasatinib is a weak time-dependent inhibitor of CYP3A4. At clinically relevant concentrations, dasatinib does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1. Dasatinib is not an inducer of human CYP enzymes.

Elimination

Elimination is primarily via the feces. Following a single oral dose of [14C]-labeled dasatinib, approximately 4% and 85% of the administered radioactivity was recovered in the urine and feces, respectively, within 10 days. Unchanged dasatinib accounted for 0.1% and 19% of the administered dose in urine and feces, respectively, with the remainder of the dose being metabolites.

Effects of Age and Gender

Pharmacokinetic analyses of demographic data indicate that there are no clinically relevant effects of age and gender on the pharmacokinetics of dasatinib.

Hepatic Impairment

Dasatinib doses of 50 mg and 20 mg were evaluated in eight patients with moderate (Child-Pugh class B) and seven patients with severe (Child-Pugh class C) hepatic impairment, respectively. Matched controls with normal hepatic function (n=15) were also evaluated and received a dasatinib dose of 70 mg. Compared to subjects with normal liver function, patients with moderate hepatic impairment had decreases in dose normalized Cmax and AUC by 47% and 8%, respectively. Patients with severe hepatic impairment had dose normalized Cmax decreased by 43% and AUC decreased by 28% compared to the normal controls.

These differences in Cmax and AUC are not clinically relevant. Dose adjustment is not necessary in patients with hepatic impairment.

Clinical Studies

Newly Diagnosed Chronic Phase CML

An open-label, multicenter, international, randomized trial was conducted in adult patients with newly diagnosed chronic phase CML. A total of 519 patients were randomized to receive either SPRYCEL 100 mg once daily or imatinib 400 mg once daily. The primary endpoint was the rate of confirmed complete cytogenetic response (CCyR) within 12 months. Confirmed CCyR was defined as a CCyR noted on two consecutive occasions (at least 28 days apart).

Median age was 46 years in the SPRYCEL group and 49 years in the imatinib groups, with 10% and 11% of patients ≥ 65 years of age. There were slightly more male than female patients in both groups (59% vs 41%). Fifty-three percent of all patients were Caucasian, and 39% were Asian. At baseline, the distribution of Hasford Scores was similar in the SPRYCEL and imatinib treatment groups (low risk: 33% and 34%; intermediate risk: 48% and 47%; high risk: 19% and 19%, respectively).

The median duration of treatment was 14 months for SPRYCEL and 14 months for imatinib. With a minimum of 12 months follow-up, 85% of patients randomized to SPRYCEL and 81% of patients randomized to imatinib were still on study.

Efficacy results are summarized in Table 6.

Table 6: Efficacy Results in Newly Diagnosed Patients with Chronic Phase CML

SPRYCEL
(n=259)
Imatinib
(n=260)
p-value
Response rate (95% CI)
Confirmed CCyR within 12 monthsa 76.8%
(71.2-81.8)
66.2%
(60. 1-7 1.9)
p=0.007*
Major Molecular Responseb 52.1%
(45.9-58.3)
33.8%
(28. 1-39.9)
p < 0.0001*
a Confirmed CCyR is defined as a CCyR noted on two consecutive occasions at least 28 days apart.
b Major molecular response (at any time) was defined as BCR-ABL ratios ≤ 0.1% by RQ-PCR in peripheral blood samples standardized on the International scale.
* Adjusted for Hasford Score and indicated statistical significance at a pre-defined nominal level of significance.
CI = confidence interval.

Median time to confirmed CCyR was 3.1 months in 199 SPRYCEL responders and 5.6 months in 177 imatinib responders. Median time to MMR was 6.3 months in 135 SPRYCEL responders and 9.2 months in 88 imatinib responders.

Five patients on the dasatinib arm progressed to either accelerated phase or blast crisis while nine patients on the imatinib arm progressed to either accelerated phase or blast crisis.

Imatinib Resistant or Intolerant CML or Ph+ ALL

The efficacy and safety of SPRYCEL were investigated in adult patients with CML or Ph+ALL whose disease was resistant to or who were intolerant to imatinib: 1158 patients had chronic phase CML, 858 patients had accelerated phase, myeloid blast phase, or lymphoid blast phase CML, and 130 patients had Ph+ ALL. In a clinical study in chronic phase CML, resistance to imatinib was defined as failure to achieve a complete hematologic response (CHR; after 3 months), major cytogenetic response (MCyR; after 6 months), or complete cytogenetic response (CCyR; after 12 months); or loss of a previous molecular response (with concurrent ≥ 10% increase in Ph+ metaphases), cytogenetic response, or hematologic response. Imatinib intolerance was defined as inability to tolerate 400 mg or more of imatinib per day or discontinuation of imatinib because of toxicity.

Results described below are based on a minimum of 2 years follow-up after the start of SPRYCEL therapy in patients with a median time from initial diagnosis of approximately 5 years. Across all studies, 48% of patients were women, 81% were white, 15% were black or Asian, 25% were 65 years of age or older, and 5% were 75 years of age or older. Most patients had long disease histories with extensive prior treatment, including imatinib, cytotoxic chemotherapy, interferon, and stem cell transplant. Overall, 80% of patients had imatinib-resistant disease and 20% of patients were intolerant to imatinib. The maximum imatinib dose had been 400-600 mg/day in about 60% of the patients and > 600 mg/day in 40% of the patients.

The primary efficacy endpoint in chronic phase CML was MCyR, defined as elimination (CCyR) or substantial diminution (by at least 65%, partial cytogenetic response) of Ph+ hematopoietic cells. The primary efficacy endpoint in accelerated phase, myeloid blast phase, lymphoid blast phase CML, and Ph+ ALL was major hematologic response (MaHR), defined as either a CHR or no evidence of leukemia (NEL).

Chronic Phase CML

Dose-Optimization Study: A randomized, open-label study was conducted in patients with chronic phase CML to evaluate the efficacy and safety of SPRYCEL administered once daily compared with SPRYCEL administered twice daily. Patients with significant cardiac diseases, including myocardial infarction within 6 months, congestive heart failure within 3 months, significant arrhythmias, or QTc prolongation were excluded from the study. The primary efficacy endpoint was MCyR in patients with imatinib-resistant CML. A total of 670 patients, of whom 497 had imatinib-resistant disease, were randomized to the SPRYCEL 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily group. Median duration of treatment was 22 months.

Efficacy was achieved across all SPRYCEL treatment groups with the once daily schedule demonstrating comparable efficacy (non-inferiority) to the twice daily schedule on the primary efficacy endpoint (difference in MCyR 1.9%; 95% CI [-6.8%-10.6%]).

Efficacy results are presented in Table 7 for patients with chronic phase CML who received the recommended starting dose of 100 mg once daily. Additional efficacy results in this patient population are described after the table. Results for all patients with chronic phase CML, regardless of dosage (a starting dosage of 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily), were consistent with those for patients treated with 100 mg once daily.

Table 7: Efficacy of SPRYCEL in Imatinib Resistant or Intolerant Chronic Phase CML

100 mg Once Daily
(n=167)
CHRa% (95% CI) 92% (86-95)
MCyRb% (95% CI) 63% (56-71)
CCyR% (95% CI) 50% (42-58)
a CHR (response confirmed after 4 weeks): WBC ≤ institutional ULN, platelets < 450,000/mm3, no blasts or promyelocytes in peripheral blood, < 5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood < 20%, and no extramedullary involvement.
b MCyR combines both complete (0% Ph+ metaphases) and partial ( > 0%-35%) responses.

In the SPRYCEL 100 mg once daily group, median time to MCyR was 2.9 months (95% CI: [2.8-3.0]). Based on the Kaplan-Meier estimates, 93% (95% CI: [88%-98%]) of patients who had achieved an MCyR maintained that response for 18 months. The estimated rate of progression-free survival and overall survival in all patients treated with 100 mg once daily was 80% (95% CI: [73%-87%]) and 91% (95% CI: [86%-96%]), respectively, at 2 years.

Advanced Phase CML and Ph+ ALL

Dose-Optimization Study: One randomized open-label study was conducted in patients with advanced phase CML (accelerated phase CML, myeloid blast phase CML, or lymphoid blast phase CML) to evaluate the efficacy and safety of SPRYCEL administered once daily compared with SPRYCEL administered twice daily. The primary efficacy endpoint was MaHR. A total of 611 patients were randomized to either the SPRYCEL 140 mg once daily or 70 mg twice daily group. Median duration of treatment was approximately 6 months for both treatment groups. The once daily schedule demonstrated comparable efficacy (non-inferiority) to the twice daily schedule on the primary efficacy endpoint.

The efficacy and safety of SPRYCEL were also investigated in patients with Ph+ ALL in one randomized study (starting dosage 140 mg once daily or 70 mg twice daily) and one single-arm study (starting dosage 70 mg twice daily). The primary efficacy endpoint was MaHR. A total of 130 patients were enrolled in these studies. The median duration of therapy was 3 months.

Response rates are presented in Table 8.

Table 8: Efficacy of SPRYCEL in Imatinib Resistant or Intolerant Advanced Phase CML and Ph+ ALL

140 mg Once Daily
Accelerated
(n=158)
Myeloid Blast
(n=75)
Lymphoid Blast
(n=33)
Ph+ALL
(n=40)
MaHRa
(95% CI)
66%
(59-74)
28%
(18-40)
42%
(26-61)
38%
(23-54)
CHRa
(95% CI)
47%
(40-56)
17%
(10-28)
21%
(9-39)
33%
(19-49)
NELa
(95% CI)
19% (13-26) 11%
(5-20)
21%
(9-39)
5%
(1-17)
MCyRb
(95% CI)
39%
(31-47)
28%
(18-40)
52%
(34-69)
70%
(54-83)
CCyR
(95% CI)
32%
(25-40)
17%
(10-28)
39%
(23-58)
50%
(34-66)
a Hematologic response criteria (all responses confirmed after 4 weeks): Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL).
CHR: WBC ≤ institutional ULN, ANC ≥ 1000/mm3, platelets ≥ 100,000/mm3, no blasts or promyelocytes in peripheral blood, bone marrow blasts ≤ 5%, < 5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood < 20%, and no extramedullary involvement.
NEL: same criteria as for CHR but ANC ≥ 500/mm3 and < 1000/mm3, or platelets ≥ 20,000/mm3 and ≤ 100,000/mm3.
b MCyR combines both complete (0% Ph+ metaphases) and partial ( > 0%-35%) responses.
CI = confidence interval ULN = upper limit of normal range.

In the SPRYCEL 140 mg once daily group, the median time to MaHR was 1.9 months for patients with accelerated phase CML, 1.9 months for patients with myeloid blast phase CML, and 1.8 months for patients with lymphoid blast phase CML.

In patients with myeloid blast phase CML, the median duration of MaHR was 8 months and 9 months for the 140 mg once daily group and the 70 mg twice daily group, respectively. In patients with lymphoid blast phase CML, the median duration of MaHR was 5 months and 8 months for the 140 mg once daily group and the 70 mg twice daily group, respectively. In patients with Ph+ ALL who were treated with SPRYCEL 140 mg once daily, the median duration of MaHR was 4.6 months. The medians of progression-free survival for patients with Ph+ ALL treated with SPRYCEL 140 mg once daily and 70 mg twice daily were 4.0 months and 3.5 months, respectively.

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999, http ://www. osha. gov/dts/osta/otm/otm_vi/otm_vi_2 .html.

3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am JHealth-Syst Pharm. (2006) 63:1172-1193.

4. Polovich M, White JM, Kelleher LO (eds). 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed). Pittsburgh, PA: Oncology Nursing Society.

 

 

Sprycel

Sprycel Medication Guide


PATIENT INFORMATION

SPRYCEL®
(Spry-sell)
(dasatinib) Tablets

Read the Patient Information that comes with SPRYCEL before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment.

What is SPRYCEL?

SPRYCEL® is a prescription medicine used to treat adults who have:

  • newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
  • Ph+ CML who no longer benefit from, or did not tolerate, other treatment, including Gleevec® (imatinib mesylate).
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatment.

It is not known if SPRYCEL is safe and effective in children younger than 18 years old.

What should I tell my healthcare provider before taking SPRYCEL?

Before you take SPRYCEL, tell your healthcare provider if you:

  • have problems with your immune system
  • have liver problems
  • have heart problems
  • are lactose intolerant
  • have any other medical conditions
  • are pregnant or planning to become pregnant. SPRYCEL may harm your unborn baby. Women should not become pregnant while taking SPRYCEL. Talk to your healthcare provider right away if you are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed. It is not known if SPRYCEL passes into your breast milk or if it can harm your baby. You and your healthcare provider should decide if you will take SPRYCEL or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, antacids, and herbal supplements.

Especially tell your healthcare provider if you take:

  • medicines that increase the amount of SPRYCEL in your bloodstream, such as:
Nizoral® (ketoconazole),
Sporanox® (itraconazole),
Norvir® (ritonavir),
Reyataz® (atazanavir sulfate),
Crixivan® (indinavir),
Viracept® (nelfmavir),
Nefazodone (serzone, nefadar),
Invirase® (saquinavir),
Ketek® (telithromycin),
E-mycin® (erythromycin),
Biaxin® (clarithromycin).
  • medicines that decrease the amount of SPRYCEL in your bloodstream, such as:
Decadron® (dexamethasone),
Dilantin® (phenytoin),
Tegretol® (carbamazepine),
Rimactane® (rifampin),
Luminal® (phenobarbital).
  • medicines whose blood levels might change by taking SPRYCEL, such as:
Sandimmune® (cyclosporine),
Alfenta® (alfentanil),
Fentanyl® (fentanyl),
Orap® (pimozide),
Rapamune® (sirolimus),
Prograf® (tacrolimus),
Ergomar® (ergotamine).

SPRYCEL is best absorbed from your stomach into your bloodstream in the presence of stomach acid. You should avoid taking medicines that reduce stomach acid, such as:

Tagamet® (cimetidine),
Pepcid® (famotidine),
Zantac® (ranitidine),
Prilosec® (omeprazole),
Protonix® (pantoprazole sodium),
Nexium® (esomeprazole),
AcipHex® (rabeprazole),
Prevacid® (lansoprazole).

Medicines that neutralize stomach acid, such as Maalox® (aluminum hydroxide/magnesium hydroxide), Turns® (calcium carbonate), or Rolaids® (calcium carbonate and magnesia), may be taken up to 2 hours before or 2 hours after SPRYCEL.

Since SPRYCEL therapy may cause bleeding, tell your healthcare provider if you are using blood thinner medicine, such as Coumadin® (warfarin sodium) or aspirin.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take SPRYCEL?

Take SPRYCEL exactly as prescribed by your healthcare provider.

  • Take SPRYCEL with or without food. Try to take SPRYCEL at the same time each day.
  • Swallow SPRYCEL tablets whole. Do not break, cut, or crush the tablets.
  • You should not drink grapefruit juice while taking SPRYCEL.
  • Your healthcare provider may:
    • change your dose of SPRYCEL or
    • tell you to temporarily stop taking SPRYCEL.
  • Do not change your dose or stop taking SPRYCEL without first talking with your healthcare provider.
  • If you miss a dose of SPRYCEL, take your next scheduled dose at its regular time. Do not take two doses at the same time. Call your healthcare provider or pharmacist if you are not sure what to do.
  • If you take too much SPRYCEL, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of SPRYCEL?

SPRYCEL may cause serious side effects, including:

  • Low Blood Cell Counts: SPRYCEL may cause low red blood cell counts (anemia), low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with SPRYCEL. Call your healthcare provider right away if you have a fever or any signs of an infection while taking SPRYCEL.
  • Bleeding: SPRYCEL may cause severe bleeding that can lead to death. Call your healthcare provider right away if you have:
    • unusual bleeding or bruising of your skin
    • bright red or dark tar-like stools
    • a decrease in your level of consciousness, headache, or change in speech.
  • Your body may hold too much fluid (fluid retention): In severe cases, fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your healthcare provider right away if you get any of these symptoms during treatment with SPRYCEL:
    • swelling all over your body
    • weight gain
    • shortness of breath and cough.
  • Heart problems. SPRYCEL may cause an abnormal heart rate, heart problems or a heart attack. Your healthcare provider will monitor the potassium and magnesium levels in your blood, and your heart function.
  • Pulmonary Arterial Hypertension (PAH). SPRYCEL may cause high blood pressure in the vessels of your lungs. PAH may happen at anytime during your treatment with SPRYCEL. Your healthcare provider should check your heart and lungs before and during your treatment with SPRYCEL. Call your healthcare provider right away if you have shortness of breath, tiredness, or swelling all over your body (fluid retention).

Other common side effects of SPRYCEL therapy include:

 

  • diarrhea
  • headache
  • cough
  • skin rash
  • fever
  • nausea
  • tiredness
  • vomiting
  • muscle pain
  • weakness
  • infections

Tell your healthcare provider 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 SPRYCEL. For more information, ask your healthcare provider or pharmacist.

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 SPRYCEL?

  • Store SPRYCEL at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Ask your healthcare provider or pharmacist about the right way to throw away outdated or unused SPRYCEL.
  • Women who are pregnant should not handle crushed or broken SPRYCEL tablets.
  • Keep SPRYCEL and all medicines out of the reach of children and pets.

General information about SPRYCEL

Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use SPRYCEL for a condition for which it is not prescribed. Do not give SPRYCEL to other people even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about SPRYCEL. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about SPRYCEL that is written for healthcare professionals.

For more information, go to www.sprycel.com or call 1-800-332-2056.

What are the ingredients in SPRYCEL?

Active ingredient: dasatinib

Inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. The tablet coating consists of hypromellose, titanium dioxide, and polyethylene glycol.

This Patient Package Insert has been approved by the U.S. Food and Drug Administration.

 

Sprycel


Sprycel Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

DASATINIB - ORAL

 

(da-SA-ti-nib)

 

COMMON BRAND NAME(S): Sprycel

 

USES: This medication is used to treat certain types of cancer (chronic myeloid leukemia and acute lymphoblastic leukemia). Dasatinib is usually used in people who are no longer benefiting from or have severe side effects due to other treatments for these diseases. It works by slowing or stopping the growth of cancer cells.

 

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using dasatinib and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth with or without food, usually once or twice daily or as directed by your doctor. This medication should be swallowed whole. Do not break, cut, or crush the tablets. Avoid taking antacids (e.g., aluminum/magnesium hydroxide, calcium carbonate) within 2 hours before or after this medication because they will decrease its effectiveness.

The dosage is based on your medical condition, lab tests, response to treatment, and other medications you may be taking. Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Since this drug can be absorbed through the skin and lungs, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

 

Sprycel


Sprycel Consumer (continued)

SIDE EFFECTS: Upset stomach, nausea, vomiting, diarrhea, headache, tiredness, and loss of appetite may occur. If these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: dry cough, swelling (especially of lower legs/the area around eyes), sudden/unexplained weight gain, increasing trouble breathing (shortness of breath).

Tell your doctor immediately if any of these rare but very serious side effects occur: black/bloody stools, dark urine, stomach/abdominal pain, vomit that looks like coffee grounds, yellowing eyes/skin.

Seek immediate medical attention if any of these rare but very serious side effects occur: severe dizziness, fainting, fast/slow/irregular heartbeat, chest pain, confusion, weakness on one side of the body.

This medication may cause very serious blood disorders (low number of blood cells such as red cells, white cells, and platelets). This effect can cause anemia, decrease your body's ability to fight an infection, or cause your body to bruise or bleed more easily. Tell your doctor immediately if you develop any of the following symptoms: signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding, unusual tiredness.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

PRECAUTIONS: Before taking dasatinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as lactose), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems, heart problems (e.g., irregular heartbeat), liver problems.

Dasatinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm (see also Drug Interactions section). Before using dasatinib, tell your doctor or pharmacist if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using dasatinib safely.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose. Wash your hands well to prevent the spread of infections.

To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Older adults may be more sensitive to the effects of this drug, especially swelling of the lower legs, sudden/unexplained weight gain, and shortness of breath.

This drug is not recommended for use during pregnancy. It may harm the unborn baby. If you become pregnant or think you may be pregnant, inform your doctor immediately. To avoid pregnancy, both males and females must use reliable form(s) of birth control (e.g., condoms, birth control pills) during treatment with this drug. Talk with your doctor about effective forms of birth control.

It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

 

Sprycel


Sprycel Consumer (continued)

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following product because very serious interactions may occur: St John's wort.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting dasatinib.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin, aspirin), H2 blockers (e.g., cimetidine, famotidine, ranitidine), proton pump inhibitors (e.g., lansoprazole, omeprazole, pantoprazole), drugs affecting liver enzymes that remove dasatinib from your body (such as azole antifungals including itraconazole/ketoconazole, corticosteroids including dexamethasone, HIV protease inhibitors including ritonavir/saquinavir, macrolide antibiotics including erythromycin, rifamycins including rifampin/rifabutin, certain anti-seizure medicines including carbamazepine/phenytoin, telithromycin).

If your doctor has prescribed low doses of aspirin to prevent heart attack or stroke (usually at dosages of 81-325 milligrams a day), you should continue to take the aspirin. Consult your doctor or pharmacist for more details.

Avoid taking this medication at the same time as antacids. Wait at least 2 hours between taking this medication and an antacid. (See also How to Use section.)

This drug can slow down the removal of other drugs from your body by affecting certain liver enzymes. These affected drugs include cyclosporine, ergotamine, fentanyl, simvastatin, and tacrolimus, among others. Ask your doctor about using these drugs safely.

Many drugs besides dasatinib may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using dasatinib, report all medications you are currently using to your doctor or pharmacist.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., magnesium/potassium blood levels, complete blood count, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

 

Sprycel

Sprycel Patient Information Including Side Effects

Brand Names: Sprycel

Generic Name: dasatinib (Pronunciation: da SAT in ib)

 

  • What is dasatinib (Sprycel)?
  • What are the possible side effects of dasatinib (Sprycel)?
  • What is the most important information I should know about dasatinib (Sprycel)?
  • What should I discuss with my health care provider before taking dasatinib (Sprycel)?
  • How should I take dasatinib (Sprycel)?
  • What happens if I miss a dose (Sprycel)?
  • What happens if I overdose (Sprycel)?
  • What should I avoid while taking dasatinib (Sprycel)?
  • What other drugs will affect dasatinib (Sprycel)?
  • Where can I get more information?

 

What is dasatinib (Sprycel)?

Dasatinib is a cancer medication that slows the growth and spread of cancer cells in the body.

Dasatinib is used to treat chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) when other cancer treatments have not been effective.

Dasatinib may also be used for other purposes not listed in this medication guide.

What are the possible side effects of dasatinib (Sprycel)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • pale skin, weakness;
  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • fever, chills, body aches, flu symptoms;
  • black, bloody, or tarry stools;
  • vomit that looks like blood or coffee grounds;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden headache, confusion, problems with vision, speech, or balance;
  • swelling in your hands, ankles, or feet; or
  • uneven heartbeats.

Less serious side effects may include:

  • headache, tiredness;
  • mild skin rash;
  • nausea, vomiting, stomach pain, diarrhea; or
  • muscle or joint pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about dasatinib (Sprycel)?

Do not use this medication without your doctor's consent if you are pregnant. It could cause harm to the unborn baby. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment.

Before using dasatinib, tell your doctor if you have liver disease, low levels of potassium or magnesium in your blood, heart disease or a heart rhythm disorder, or if you have a personal or family history of "Long QT syndrome."

Do not crush, chew, or break a dasatinib tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

There are many other medicines that can interact with dasatinib. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Dasatinib can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. It is important that you not miss any scheduled visits to your doctor.

Avoid contact with people who have colds, the flu, or other contagious illnesses. Contact your doctor immediately if you develop signs of infection.

Related Drug Centers
  • Sprycel

 

Sprycel

Sprycel Patient Information including How Should I Take

In this Article

  • What is dasatinib (Sprycel)?
  • What are the possible side effects of dasatinib (Sprycel)?
  • What is the most important information I should know about dasatinib (Sprycel)?
  • What should I discuss with my health care provider before taking dasatinib (Sprycel)?
  • How should I take dasatinib (Sprycel)?
  • What happens if I miss a dose (Sprycel)?
  • What happens if I overdose (Sprycel)?
  • What should I avoid while taking dasatinib (Sprycel)?
  • What other drugs will affect dasatinib (Sprycel)?
  • Where can I get more information?

What should I discuss with my health care provider before taking dasatinib (Sprycel)?

You should not use dasatinib if:

  • you have not first received a medication called imatinib (Gleevec); or
  • if you are pregnant or planning to become pregnant during treatment with dasatinib.

If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before using dasatinib, tell your doctor if you have:

  • liver disease;
  • low levels of potassium or magnesium in your blood;
  • heart disease or a heart rhythm disorder; or
  • a personal or family history of "Long QT syndrome."

FDA pregnancy category D. This medication can cause harm to an unborn baby. Do not use dasatinib without telling your doctor if you are pregnant. Tell your doctor if you become pregnant during treatment.

Use birth control to prevent pregnancy while you are taking dasatinib, whether you are a man or a woman. Dasatinib use by either parent may cause birth defects. If you are a man taking dasatinib, use a condom during any sexual activity.

It is not known whether dasatinib passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Taking dasatinib may affect your ability to have children whether you are a man or a woman. Talk to your doctor about your specific risk.

Dasatinib tablets contain lactose. Talk to your doctor before using this medication if you are lactose-intolerant.

How should I take dasatinib (Sprycel)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

This medicine is usually taken once in the morning and once in the evening. Follow your doctor's instructions. You may take the medication with or without food.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Do not crush, chew, or break a dasatinib tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

Do not use a tablet that has been accidentally broken. The medicine from a crushed or broken tablet can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If you must handle a broken tablet, ask your doctor or pharmacist how to safely handle and dispose of the tablet.

Dasatinib can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. It is important that you not miss any scheduled visits to your doctor.

Store dasatinib at room temperature away from moisture and heat.

Related Drug Centers
  • Sprycel

Sprycel

Sprycel Patient Information including If I Miss a Dose

In this Article

  • What is dasatinib (Sprycel)?
  • What are the possible side effects of dasatinib (Sprycel)?
  • What is the most important information I should know about dasatinib (Sprycel)?
  • What should I discuss with my health care provider before taking dasatinib (Sprycel)?
  • How should I take dasatinib (Sprycel)?
  • What happens if I miss a dose (Sprycel)?
  • What happens if I overdose (Sprycel)?
  • What should I avoid while taking dasatinib (Sprycel)?
  • What other drugs will affect dasatinib (Sprycel)?
  • Where can I get more information?

What happens if I miss a dose (Sprycel)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Sprycel)?

Seek emergency medical attention if you think you have used too much of this medicine. Symptoms of a dasatinib overdose are unknown.

What should I avoid while taking dasatinib (Sprycel)?

Avoid using antacids without your doctor's advice while you are taking dasatinib. Use only the specific type of antacid your doctor recommends. Antacids contain different medicines and some types can make it harder for your body to absorb dasatinib.

If you take an antacid, take it at least 2 hours before or 2 hours after taking dasatinib.

Avoid contact with people who have colds, the flu, or other contagious illnesses. Contact your doctor immediately if you develop signs of infection.

What other drugs will affect dasatinib (Sprycel)?

Before taking dasatinib, tell your doctor if you are using any of the following drugs:

  • a blood thinner such as warfarin (Coumadin);
  • fentanyl (Actiq, Duragesic, Fentora)
  • heart rhythm medication;
  • nefazodone (Serzone);
  • rifabutin (Mycobutin);
  • rifampin (Rifater, Rifamate, Rimactane)
  • dexamethasone (Decadron, Hexadrol);
  • St. John's wort;
  • cisapride (Propulsid), pimozide (Orap);
  • quinidine (Cardioquin, Quinidex, Quinaglute);
  • sirolimus (Rapamune), tacrolimus (Prograf);
  • cyclosporine (Neoral, Sandimmune, Gengraf);
  • HIV medicine such as atazanavir (Reyataz), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Invirase), nelfinavir (Viracept);
  • ketoconazole (Nizoral) or itraconazole (Sporanox);
  • antibiotics such as erythromycin (E-Mycin, Ery-Tab, E.E.S.), telithromycin (Ketek), or clarithromycin (Biaxin);
  • seizure medication such as carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital (Luminal, Solfoton);
  • ergot medicine such as methysergide (Sansert), ergotamine (Ergomar), dihydroergotamine (D.H.E., Migranal Nasal Spray); or
  • stomach acid reducers such as cimetidine (Tagamet), esomeprazole (Nexium), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), rabeprazole (Aciphex), or ranitidine (Zantac).

This list is not complete and there may be other drugs that can interact with dasatinib. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about dasatinib.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2010 Cerner Multum, Inc. Version: 1.08. Revision date: 08/03/2009.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

 

Related Drug Centers
  • Sprycel
Share
 
Ruai Pharm Stats